Patch for treating breast cancer chest wall metastasis through combination of anti-angiogenesis inhibitor and chemotherapeutic drug

Abstract

The invention relates to a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapeutic drug. The patch comprises a backing layer and a medicine storage layer, and the medicine storage layer is arranged on the inner side face of the backing layer. Wherein the medicine storage layer comprises an anti-tumor medicine, an anti-angiogenesis inhibitor and a slow-release agent. According to the patch provided by the invention, the anti-tumor drug, the anti-angiogenesis inhibitor and the sustained-release agent are arranged, so that the patch not only can play roles in isolating cancerous wounds and preventing bleeding, infection, peculiar smell and the like, but also has anti-tumor and anti-cancer effects, so that the drug properties of the anti-tumor drug and the anti-angiogenesis inhibitor can be slowly released; in this way, focuses can be effectively positioned, cancer cells can be killed, local tissue can be repaired and reconstructed while treatment is conducted, and metabolism is promoted. Meanwhile, compared with other treatment modes, the patch treatment mode can be accepted by patients more easily, and long-term treatment of the patients is facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of medicine, and in particular to a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug. Background Art

[0002] Breast cancer is a common, frequently occurring disease among young and middle-aged women, causing great pain to a large number of women. Common treatments include long-term treatment with radiation, chemotherapy, and drugs. Neither Chinese nor Western medicine can guarantee that there will be no recurrence. Western medicine has significant side effects, and traditional decoctions are inconvenient to prepare and require a long course of treatment. It is difficult for patients to adhere to long-term medication, resulting in recurring disease and delay in the best time for treatment.

[0003] Peritoneal metastasis of breast cancer is a type of breast cancer. Its incidence is relatively low, but once it occurs, it has a significant impact on the patient's survival. According to literature reports, peritoneal metastasis mainly occurs in patients with colorectal cancer, appendix cancer, gastric cancer, or ovarian cancer, while most cases of peritoneal metastasis of breast cancer are related to metastasis to other sites, and peritoneal metastasis usually occurs later than metastasis to other sites. The prevalence of peritoneal metastasis of breast cancer is between 0.5% and 0.7%. In a large sample study, data on 5,791 cases of peritoneal metastasis were collected over an 18-year period, and it was found that the overall median survival of patients with peritoneal metastasis of breast cancer was 68.4 months; the median time from the initial diagnosis of breast cancer to the occurrence of peritoneal metastasis was 59.5 months.

[0004] Because peritoneal metastasis of breast cancer is relatively rare and its clinical manifestations lack specificity, the interval from primary cancer to metastasis is long, which increases the risk of misdiagnosis in pathology and clinical practice, making it more difficult to treat. In addition, the difficulty in treating peritoneal metastasis lies in the lack of targeted drugs and the difficulty of drugs to cross the blood-peritoneal barrier, resulting in poor results of systemic chemotherapy. For patients with peritoneal metastasis of breast cancer, treatment is usually limited to chemotherapy or hormone therapy, and the treatment method of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is generally applicable to peritoneal cancer caused by digestive tract or female reproductive system cancers, but there are no clear guidelines for the treatment of peritoneal cancer caused by breast cancer.

[0005] The use of patches to treat breast cancer peritoneal metastasis is a new method for breast cancer treatment. Compared with conventional treatments, most patients can adhere to patch treatment for a long time. The application scenarios of breast cancer abdominal wall metastasis patches are mainly reflected in the following aspects:

[0006] Relieve symptoms and improve quality of life: For patients with abdominal wall metastasis of breast cancer, the patch can be used to relieve symptoms such as pain and swelling, thereby improving the patient's quality of life;

[0007] Adjuvant therapy: In some cases, patches can be used as an adjunct to chemotherapy or other treatments to help improve treatment outcomes. For example, there are reports that continued oral administration of Chinese medicine and topical plasters during chemotherapy can help improve symptoms and signs and enhance confidence in survival.

[0008] Local treatment: For breast cancer patients with local abdominal wall metastasis, the patch may be used as a local treatment method to directly act on the metastatic site to relieve local symptoms and control local disease progression;

[0009] Part of a comprehensive treatment strategy: In the comprehensive treatment of breast cancer abdominal wall metastasis, the patch may be used in combination with other treatments (such as surgery, chemotherapy, radiotherapy, etc.) as part of a multimodal treatment strategy to achieve better therapeutic effects.

[0010] However, in the prior art, general patches or dressings can only isolate cancerous wounds and prevent bleeding, infection, odor, etc., and the drugs in such patches or dressings diffuse relatively quickly, which is not conducive to the treatment of breast cancer.

[0011] CN 114159229 A discloses a special dressing for cancerous wounds, comprising: a fixing layer and a functional layer; the fixing layer is a PE anti-allergic fixing film with viscose on its surface; the functional layer is attached to the cancerous wound, and comprises from top to bottom: a buffer layer, an activated carbon fiber layer, and a functional combination layer; the buffer layer is a thin foam layer; the activated carbon fiber layer is a thin sheet of activated carbon fiber impregnated with tea polyphenols; the functional combination layer is a combination of alginate fiber thin sheets and porous water-absorbing materials. The dressing has the effects of analgesia, anti-infiltration, antibacterial and deodorization for cancerous wounds, and is not only suitable for the care of cancerous wounds, but also for the care of other wounds accompanied by pain, odor, large amounts of exudate and easy infection. However, the dressing only plays the role of isolating cancerous wounds, preventing bleeding, infection, odor, etc., and cannot play the role of anti-tumor and anti-cancer.

[0012] CN 1655772 B discloses a transdermal therapeutic system having a cover layer and an adhesive matrix containing fentanyl. However, fentanyl has a small therapeutic range and has the potential to be addictive like all opioids.

[0013] Therefore, how to come up with a patch that can fight cancer, slowly release drug properties, effectively locate lesions, kill cancer cells and not easily cause dependence has become a problem that needs to be solved urgently. Summary of the invention

[0014] In view of this, the present invention provides a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with chemotherapy drugs. By setting anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents, the patch can fight cancer, slowly release drug properties, effectively locate lesions, kill cancer cells and is not easy to cause dependence.

[0015] Specifically, the present invention is achieved through the following technical solutions:

[0016] A patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug, comprising a backing layer and a drug reservoir layer, wherein the drug reservoir layer is arranged on the inner side of the backing layer;

[0017] The drug reservoir layer includes anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents.

[0018] In the present invention, the sustained-release agent is used to drive the slow release of anti-tumor drugs and anti-angiogenesis inhibitors.

[0019] As an optional embodiment, in the drug reservoir layer, the mass ratio of the anti-tumor drug, the anti-angiogenesis inhibitor and the sustained-release agent is 1:0.8-1.2:0.8-1.2, preferably 1:1:1.

[0020] As an optional embodiment, the anti-tumor drug includes at least one of the following or a combination thereof: a chemotherapeutic drug, a targeted drug and an endocrine drug.

[0021] As an optional embodiment, the chemotherapy drug includes at least one of capecitabine and vinorelbine.

[0022] As an optional embodiment, the targeted drug includes at least one of trastuzumab and a tyrosinase inhibitor, for example, the tyrosinase inhibitor may be pyrotinib.

[0023] As an optional embodiment, the endocrine drug includes at least one of a selective estrogen receptor modulator, an estrogen receptor blocker, an aromatase inhibitor, tamoxifen, a CDK4 inhibitor and a CDK6 inhibitor.

[0024] As an optional embodiment, the CDK4 inhibitor and the CDK6 inhibitor are used in combination, which is referred to as a CDK4 / 6 inhibitor.

[0025] As an optional embodiment, the anti-angiogenesis inhibitor includes at least one of a biomacromolecule drug targeting VEGF (vascular endothelial growth factor), VEGFR (vascular endothelial growth factor receptor, also known as tyrosine kinase receptor), and a small molecule VEGFR tyrosine kinase inhibitor.

[0026] Optionally, the biomacromolecule drug targeting VEGF and VEGFR includes at least one of bevacizumab and ramucirumab.

[0027] Optionally, the small molecule VEGFR tyrosine kinase inhibitor includes at least one of apatinib, sorafenib and sunitinib.

[0028] As an optional embodiment, the sustained-release agent includes nanosilver.

[0029] As an optional embodiment, the drug reservoir layer is disposed at the center of the inner side of the backing layer.

[0030] As an optional embodiment, the backing layer and the drug reservoir layer are circular, rectangular or other shapes.

[0031] As an optional embodiment, the area of ​​the backing layer is larger than the area of ​​the drug reservoir layer.

[0032] As an optional embodiment, the thickness of the backing layer is greater than the thickness of the drug reservoir layer.

[0033] As an optional embodiment, the patch further includes a protective layer, which is disposed at least on the side of the drug reservoir layer away from the backing layer, for protecting the drug in the drug reservoir layer to prevent it from being contaminated or the drug from being lost or leaked, thereby affecting its efficacy on breast cancer lesions.

[0034] In the existing technology, endocrine drugs are mainly suitable for patients with HR-positive breast cancer, while targeted drugs and chemotherapy anti-angiogenic drugs are suitable for a wider range of patient groups, including HER2-positive and triple-negative breast cancer. However, from the perspective of side effects and compliance, the side effects of endocrine therapy are relatively small and the patient compliance is better; chemotherapy anti-angiogenic drugs may have more side effects, such as hypertension, hand-foot syndrome, etc.

[0035] The patch of the present invention is an integrated patch containing anti-tumor drugs (i.e., targeted drugs), endocrine drugs, anti-angiogenesis inhibitors, slow release technology, and fusion anti-tumor and local dressings. Its main technical characteristics are: on the basis of the current common patch, anti-tumor drugs and endocrine drugs are added, and the drugs are slowly released to achieve anti-tumor and also isolate the effect of cancerous wounds. Specifically, targeted drugs mainly act on specific molecular targets, endocrine drugs affect tumor growth by regulating hormone levels, and chemotherapy anti-angiogenesis inhibitor drugs mainly control tumors by inhibiting tumor angiogenesis. The present invention comprehensively utilizes the advantages of anti-tumor drugs (i.e., targeted drugs), endocrine drugs and anti-angiogenesis inhibitors, combined with slow release technology, and the obtained anti-angiogenesis inhibitor combined with chemotherapy drugs for the treatment of breast cancer chest wall metastasis can be anti-cancer, slowly release drug properties, effectively locate lesions, kill cancer cells, and is not easy to make people dependent.

[0036] In the present invention, the patch is applied to the local area of ​​the ulcerated wound, which not only has the anti-tumor drug acting on the tumor tissue, but also has the function of protecting the wound as a local dressing.

[0037] The technical solution provided by the present invention has at least the following beneficial effects compared with the prior art:

[0038] (1) The anti-angiogenesis inhibitor combined with chemotherapy drugs provided by the present invention for treating breast cancer chest wall metastasis can not only isolate cancerous wounds and prevent bleeding, infection, odor, etc. by setting anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents, but also has anti-tumor and anti-cancer effects, and can slowly release the anti-tumor drugs, so that the lesions can be effectively located and cancer cells can be killed. At the same time, the patch treatment method can be repaired and rebuilt, and the metabolism can be promoted. At the same time, compared with other treatment methods, the patch treatment method can make patients more acceptable and is conducive to long-term treatment of patients;

[0039] (2) The anti-angiogenesis inhibitor combined with chemotherapy drugs provided by the present invention for treating breast cancer chest wall metastasis patches, by using nanosilver as a sustained-release agent and a nano-delivery system to treat breast cancer, can improve the targeting and efficacy of drugs, reduce toxic side effects, enhance drug penetration, enhance immune response, achieve controlled release of drugs, reduce drug resistance, and help improve the efficacy of synergistic treatment with other treatment methods;

[0040] (3) The breast cancer chest wall metastasis local patch provided by the present invention has a deep anti-tumor effect by effectively penetrating the local tissue, and has the characteristics of strong penetration and direct access to the lesion;

[0041] (4) The local patch for breast cancer chest wall metastasis provided by the present invention is beneficial to accelerate drug absorption, prevent odor, and has the characteristics of rapid onset of action;

[0042] (5) The breast cancer chest wall metastasis local patch provided by the present invention is easy to absorb and aggregate at the lesion, deeply care, and control bleeding, and has the characteristics of strong adsorption; the patch has strong medicinal power, definite therapeutic effect, and has the characteristics of high cure rate;

[0043] (6) The local patch for breast cancer chest wall metastasis provided by the present invention can repair and rebuild local tissues and promote metabolism while treating the symptoms and the root causes. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0045] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or related technical descriptions are briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0046] Figure 1 This is a schematic diagram of the structure of a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug according to an embodiment of the present invention.

[0047] The figures are marked as follows: 1-backing layer, 2-drug reservoir layer, 3-protective layer. DETAILED DESCRIPTION

[0048] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are 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 creative work are within the scope of protection of the present invention.

[0049] See also Figure 1 Some embodiments of the present invention provide a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug, comprising a backing layer 1 and a drug reservoir layer 2. The drug reservoir layer 2 is arranged on the inner side of the backing layer 1; wherein the drug reservoir layer 2 comprises an anti-tumor drug, an anti-angiogenesis inhibitor and a sustained-release agent, and the sustained-release agent is used to drive the slow release of the anti-tumor drug and the anti-angiogenesis inhibitor.

[0050] The patch for treating breast cancer chest wall metastasis by combining anti-angiogenesis inhibitors and chemotherapy drugs provided in an embodiment of the present invention comprises a backing layer 1 and a drug reservoir layer 2. The drug reservoir layer 2 is provided with anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents, so that tumors and cancers can be treated by the patch, and tumor growth can be inhibited, and tumor metastasis and recurrence can be prevented. At the same time, by arranging a sustained-release agent in the patch, the anti-tumor drug can be slowly released, which is more conducive to the treatment of tumors and breast cancer. Compared with other treatment methods, the patch treatment method can make patients more acceptable and is conducive to long-term treatment of patients.

[0051] In the present invention, the components of the anti-tumor drug, the anti-angiogenesis inhibitor and the sustained-release agent can be prepared in a certain ratio.

[0052] In some embodiments, in the drug reservoir layer, the mass ratio of the anti-tumor drug, the anti-angiogenesis inhibitor and the sustained-release agent is 1:0.8-1.2:0.8-1.2, for example, 1:1:1.

[0053] In the present invention, the anti-tumor drug, anti-angiogenesis inhibitor and sustained-release agent may also be prepared according to other ratios, which may be specifically set according to actual conditions.

[0054] In some embodiments, the anti-tumor drug includes at least one of the following or a combination thereof: a chemotherapeutic drug, a targeted drug, and an endocrine drug.

[0055] Specifically, in this embodiment, the anti-tumor drug includes at least one of the following or a combination thereof: chemotherapy drugs, targeted drugs and endocrine drugs. The anti-tumor drug may also be other anti-tumor drugs, which may be set according to actual conditions.

[0056] In some embodiments, the chemotherapy drug includes at least one of capecitabine and vinorelbine.

[0057] In some embodiments, the targeted drug includes at least one of trastuzumab and a tyrosinase inhibitor, for example, the tyrosinase inhibitor may be pyrotinib.

[0058] The present invention adopts the targeted drug to treat tumors. Targeted therapy can kill tumor cells efficiently and selectively with lower adverse reactions, and is a very promising treatment plan in tumor treatment.

[0059] In some embodiments, the endocrine drug includes at least one of a selective estrogen receptor modulator, an estrogen receptor blocker, an aromatase inhibitor, tamoxifen, a CDK4 inhibitor, and a CDK6 inhibitor.

[0060] In the present invention, CDK4 inhibitors and CDK6 inhibitors are cell cycle arrest drugs used to inhibit cyclin-dependent kinases (CDKs). In some embodiments, the CDK4 inhibitor and CDK6 inhibitor are used in combination and are referred to as CDK4 / 6 inhibitors.

[0061] The present invention uses endocrine drugs to treat endocrine metabolic abnormalities in patients during breast cancer chest wall metastasis. Endocrine therapy is suitable for patients with hormone receptor-positive (HR-positive) breast cancer, which can reduce the risk of recurrence of early breast cancer and prolong the progression-free survival of recurrent and metastatic breast cancer. Since there are many types of endocrine drugs to choose from, it has the characteristics of diversified drug types. In addition, since endocrine therapy has mild adverse reactions and has little impact on the quality of life of patients, it occupies a very important position in the treatment of HR-positive breast cancer and has good efficacy and safety.

[0062] In some embodiments, the anti-angiogenesis inhibitor includes at least one of a biomacromolecule drug targeting VEGF and VEGFR and a small molecule VEGFR tyrosine kinase inhibitor.

[0063] In the present invention, the anti-angiogenesis inhibitor inhibits the binding of VEGF to VEGFR and regulates angiogenesis-related signaling pathways, thereby inhibiting angiogenesis and achieving the purpose of controlling tumor growth and metastasis.

[0064] Optionally, the biomacromolecule drug targeting VEGF and VEGFR includes at least one of bevacizumab and ramucirumab, etc.; the small molecule VEGFR tyrosine kinase inhibitor includes at least one of apatinib, sorafenib and sunitinib, etc.

[0065] Specifically, humanized monoclonal antibodies (represented by bevacizumab) or small molecule tyrosinase inhibitors targeting vascular endothelial growth factor (VEGF) can inhibit tumor angiogenesis. Bevacizumab is a humanized monoclonal antibody targeting VEGF, which has high affinity and specifically binds to VEGF to inhibit tumor angiogenesis. Small molecule VEGFR tyrosine kinase inhibitors are small molecule drugs that act on VEGFR. They have inhibitory effects on some tyrosine kinases, can penetrate cell membranes, and target specific sites of tumor cells and surrounding endothelial and vascular kinase receptors, thereby blocking cell proliferation signal transduction pathways, and have multi-target effects. For example, apatinib belongs to this type of small molecule targeted drug, and its target is VEGFR. Apatinib can highly selectively bind to vascular endothelial growth factor receptor 2 (VEGFR2), block signal transduction, and effectively resist tumor angiogenesis, thereby inhibiting tumor growth, metastasis and spread.

[0066] The present invention uses an anti-angiogenesis inhibitor drug combined with a chemotherapy drug for recurrent or metastatic HER-2 negative advanced breast cancer, and has initially demonstrated efficacy.

[0067] In some embodiments, the sustained release agent comprises nanosilver.

[0068] In this embodiment, the sustained-release agent includes nanosilver, so that the anti-tumor drug and anti-angiogenesis inhibitor can be processed into the form of "nanosilver ions" through nanosilver ion technology, and the "nanosilver ions" can be penetrated through the local tumor tissue and located in the lesion by setting the ion permeameter with different wavelengths and waveforms of medium-frequency currents to kill tumor cells, and effectively repair damaged epithelial cells to allow local tissues to grow again. Of course, the sustained-release agent can also include other ingredients with sustained-release effects, which are not limited here.

[0069] The present invention uses nanosilver as a sustained-release agent for the treatment of breast cancer, especially abdominal wall metastasis. By using a nano delivery system, the targeted drug is slowly and continuously applied to the breast cancer lesion to improve the treatment of breast cancer and enhance the therapeutic effect of breast cancer.

[0070] In some embodiments, the drug reservoir layer 2 is disposed at the center of the inner side of the backing layer 1 .

[0071] In some embodiments, the backing layer 1 and the drug reservoir layer 2 are both circular, and the diameter of the backing layer 1 is larger than the diameter of the drug reservoir layer 2 .

[0072] In some embodiments, the backing layer 1 is rectangular.

[0073] In some embodiments, the thickness of the backing layer 1 is greater than the thickness of the drug reservoir layer 2 .

[0074] In some embodiments, the patch further comprises a protective layer 3, which is disposed at least on the side of the drug reservoir layer 2 away from the backing layer 1, and is used to protect the drug in the drug reservoir layer 2 to prevent it from being contaminated or the drug from being lost or leaked, thereby affecting its efficacy on breast cancer lesions.

[0075] The present application will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods in the following examples that do not specify specific conditions are usually measured according to national standards. If there is no corresponding national standard, then carry out according to general international standards, normal conditions, or according to the conditions recommended by the manufacturer. Unless otherwise specified, the various raw materials, reagents, etc. used in the present application can be purchased from the market or can be prepared by existing methods.

[0076] Example 1

[0077] A patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with chemotherapy drugs, comprising a backing layer 1, a drug reservoir layer 2 and a protective layer 3; the drug reservoir layer 2 is arranged on the inner side of the backing layer 1 for storing drugs; the protective layer 3 is arranged on the side of the drug reservoir layer 2 away from the backing layer 1 for protecting the drugs in the drug reservoir layer 2; the backing layer 1 and the drug reservoir layer 2 are both circular, and the diameter of the backing layer 1 is greater than the diameter of the drug reservoir layer 2;

[0078] Among them, the drug reservoir layer 2 includes anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents, wherein the anti-tumor drugs include the chemotherapy drug capecitabine, the targeted drug trastuzumab and the endocrine drug tamoxifen in a mass ratio of 1:1:1; the anti-angiogenesis inhibitors include monoclonal antibody targeted drugs and tyrosinase inhibitors in a mass ratio of 1:1; the sustained-release agent is nanosilver, which is used to drive the slow release of anti-tumor drugs and anti-angiogenesis inhibitors; the mass ratio of anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents is 1:1:1.

[0079] Example 2

[0080] A patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug, comprising a backing layer 1, a drug reservoir layer 2 and a protective layer 3; the drug reservoir layer 2 is arranged on the inner side of the backing layer 1 for storing drugs; the protective layer 3 is arranged on the side of the drug reservoir layer 2 away from the backing layer 1 for protecting the drugs in the drug reservoir layer 2; the backing layer 1 and the drug reservoir layer 2 are both rectangular, and the diameter of the backing layer 1 is greater than the diameter of the drug reservoir layer 2;

[0081] Among them, the drug reservoir layer 2 includes anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents. The anti-tumor drugs include the chemotherapy drug capecitabine, the targeted drug trastuzumab and the endocrine drug tamoxifen in a mass ratio of 1:1:1; the anti-angiogenesis inhibitors include monoclonal antibody targeted drugs and tyrosinase inhibitors in a mass ratio of 1:1; the sustained-release agent is nanosilver, which is used to drive the slow release of anti-tumor drugs and anti-angiogenesis inhibitors; the mass ratio of anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents is 1:1:1.

[0082] Comparative Example 1

[0083] This comparative example provides a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with a chemotherapy drug. The difference between the other examples 1 is that the drug reservoir layer 2 does not include a corrosion inhibitor, that is, the drug reservoir layer 2 includes an anti-tumor drug and an anti-angiogenesis inhibitor, the anti-tumor drug includes a chemotherapy drug capecitabine, a targeted drug trastuzumab and an endocrine drug tamoxifen in a mass ratio of 1:1:1; the anti-angiogenesis inhibitor includes a monoclonal antibody targeted drug and a tyrosinase inhibitor in a mass ratio of 1:1; the mass ratio of the anti-tumor drug to the anti-angiogenesis inhibitor is 1:1.

[0084] Comparative Example 2

[0085] This comparative example provides a patch for treating breast cancer chest wall metastasis by combining an anti-angiogenesis inhibitor with chemotherapy drugs. The difference between the other embodiments 2 is that the drug reservoir layer 2 does not include a corrosion inhibitor, that is, the drug reservoir layer 2 includes an anti-tumor drug and an anti-angiogenesis inhibitor, the anti-tumor drug includes a chemotherapy drug capecitabine, a targeted drug trastuzumab and an endocrine drug tamoxifen in a mass ratio of 1:1:1; the anti-angiogenesis inhibitor includes a monoclonal antibody targeted drug and a tyrosinase inhibitor in a mass ratio of 1:1; the mass ratio of the anti-tumor drug to the anti-angiogenesis inhibitor is 1:1.

[0086] Effects of the patch

[0087] The anti-angiogenesis inhibitor combined with chemotherapy drugs for treating breast cancer chest wall metastasis patches provided in Examples 1-2 and Comparative Examples 1-2 are used for the treatment of patients with breast cancer abdominal wall metastasis. Compared with Examples 1 and 2, in Comparative Examples 1 and 2, since the breast cancer chest wall metastasis patches do not contain corrosion inhibitors, they cannot drive the slow release of anti-tumor drugs and anti-angiogenesis inhibitors, resulting in the use of high-concentration drugs that are likely to cause toxic side effects to patients, and long-term use is likely to cause drug resistance in the patient's body, reducing the therapeutic efficacy; at the same time, since the targeted drugs cannot be slowly released, the service life of the patch is short, and the patch needs to be replaced frequently for continuous treatment.

[0088] In Examples 1 and 2, since the breast cancer chest wall metastasis patch contains corrosion inhibitor nanosilver, the patch can improve the targeting and efficacy of drugs, reduce toxic side effects, enhance drug penetration, enhance immune response, achieve controlled release of drugs, reduce drug resistance and achieve synergistic treatment effects in the treatment of breast cancer through a nano delivery system.

[0089] The anti-angiogenesis inhibitor combined with chemotherapy drugs provided by the present invention for treating breast cancer chest wall metastasis has the following beneficial effects in the treatment of breast cancer:

[0090] Improved local drug concentration: The patch can directly act on the local area of ​​breast cancer abdominal wall metastasis, thereby achieving high local drug concentration, which is very beneficial for site-specific drug delivery;

[0091] Reduced systemic side effects: Since patches can achieve local high-concentration drug delivery, they can reduce the systemic distribution of drugs, thereby reducing systemic side effects; this is beneficial to improving patients' quality of life and treatment tolerance;

[0092] Reduction of tumor volume and cancer biomarkers: Application of the breast cancer chest wall metastasis patch significantly reduced tumor volume compared with oral anticancer drugs;

[0093] Improve the convenience and compliance of treatment: As a transdermal drug delivery method, breast cancer chest wall transfer patch can provide a more convenient treatment option. Patients can use it at home, which may improve treatment compliance.

[0094] Potential synergistic therapeutic effects: The breast cancer chest wall metastasis patch can produce synergistic effects with other treatment methods (such as chemotherapy, targeted therapy or immunotherapy) to enhance the therapeutic effect.

[0095] In summary, the use of breast cancer chest wall metastasis patches in patients with breast cancer abdominal wall metastasis can bring benefits such as high local drug concentration, reduced systemic side effects, reduced tumor volume and cancer biomarkers, and improved treatment convenience and compliance.

[0096] Although this specification includes many specific implementation details, these should not be interpreted as limiting the scope of any invention or the scope of protection claimed, but are mainly used to describe the features of the specific embodiments of specific inventions. Certain features described in multiple embodiments in this specification may also be implemented in combination in a single embodiment. On the other hand, the various features described in a single embodiment may also be implemented separately in multiple embodiments or in any suitable sub-combination. In addition, although features may work in certain combinations as described above and even initially claim protection, one or more features from the claimed combination may be removed from the combination in some cases, and the claimed combination may point to a sub-combination or a variation of a sub-combination.

[0097] Thus, specific embodiments of the subject matter have been described. Other embodiments are within the scope of the appended claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve the desired results. In addition, the processes depicted in the drawings do not necessarily require the particular order or sequential order shown to achieve the desired results. In some implementations, multitasking and parallel processing may be advantageous.

[0098] It should be noted that, in this article, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0099] The foregoing is merely a specific embodiment of the present invention, which enables those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A patch for treating breast cancer chest wall metastasis using an anti-angiogenesis inhibitor combined with a chemotherapeutic drug, characterized in that: include: Backing layer (1); A drug reservoir layer (2) is arranged on the inner side of the backing layer (1); Wherein, the drug reservoir layer (2) comprises anti-tumor drugs, anti-angiogenesis inhibitors and sustained-release agents.

2. The patch according to claim 1, characterized in that The mass ratio of the anti-tumor drug, the anti-angiogenesis inhibitor and the sustained-release agent is 1:0.8-1.2:0.8-1.

2.

3. The patch according to claim 2, characterized in that The anti-tumor drug comprises at least one of the following or a combination thereof: Chemotherapy drugs, targeted drugs and endocrine drugs.

4. The patch according to claim 3, characterized in that The chemotherapy drug comprises at least one of capecitabine and vinorelbine; or / and The targeted drug comprises at least one of trastuzumab and a tyrosinase inhibitor; or / and The endocrine drug includes at least one of a selective estrogen receptor modulator, an estrogen receptor blocker, an aromatase inhibitor, tamoxifen, a CDK4 inhibitor and a CDK6 inhibitor.

5. The patch according to claim 1, characterized in that The anti-angiogenesis inhibitor includes at least one of a biomacromolecule drug targeting VEGF and VEGFR and a small molecule VEGFR tyrosine kinase inhibitor; or / and The sustained-release agent includes nanosilver.

6. The patch according to claim 5, characterized in that The biomacromolecule drug targeting VEGF and VEGFR includes at least one of bevacizumab and ramucirumab; The small molecule VEGFR tyrosine kinase inhibitor includes at least one of apatinib, sorafenib and sunitinib.

7. The patch according to any one of claims 1 to 6, characterized in that The drug reservoir layer (2) is arranged at the center of the inner side of the backing layer (1).

8. The patch according to any one of claims 1 to 6, characterized in that The backing layer (1) and the drug reservoir layer (2) are circular or rectangular.

9. The patch according to any one of claims 1 to 6, characterized in that The area of ​​the backing layer (1) is greater than the area of ​​the drug reservoir layer (2); or / and the thickness of the backing layer (1) is greater than the thickness of the drug reservoir layer (2).

10. The patch according to any one of claims 1 to 6, characterized in that Also includes: The protective layer (3) is at least arranged on the side of the drug reservoir layer (2) facing away from the backing layer (1).

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