CN113116884A - Application of nobiletin in preparation of medicine for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicine - Google Patents
Application of nobiletin in preparation of medicine for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicine Download PDFInfo
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- CN113116884A CN113116884A CN202110458778.7A CN202110458778A CN113116884A CN 113116884 A CN113116884 A CN 113116884A CN 202110458778 A CN202110458778 A CN 202110458778A CN 113116884 A CN113116884 A CN 113116884A
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- chemotherapeutic agent
- nobiletin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
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Abstract
The invention relates to application of nobiletin in preparing a medicament for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicaments. By the application method disclosed in the application, the nobiletin can be used for preventing or treating skin tissue diseases or symptoms related to the administration of the chemotherapeutic drug in a subject, and the use of the nobiletin can effectively control the side effects of the skin caused by the chemotherapeutic drug. The research of the invention finds that, at the cellular level, the nobiletin can relieve the negative effect of the prodrug 5-fluorouracil of capecitabine on cell proliferation. On the animal level, the nobiletin can obviously prevent the capecitabine induced hand-foot syndrome of rats.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of nobiletin in preparation of a medicine for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic drugs.
Background
Chemotherapy is currently one of the major approaches to cancer treatment. Chemotherapy drugs can also damage normal tissues of patients while killing cancer cells, so chemotherapy often causes serious side effects, especially those occurring on the skin. Severe skin side effects from chemotherapy can impair the quality of life of patients, cause reduced tolerance to medication for patients, and thereby adversely affect the therapeutic effect, lead to disease progression, and further affect the survival of patients.
Capecitabine is a common anticancer drug, is mainly used for treating advanced breast cancer and colorectal cancer, and can be used for rescuing and treating breast cancer after anthracyclines and taxus treatment failure. However, capecitabine administration has certain adverse effects, for example, capecitabine administration easily causes skin swelling and erythema, blisters or severe pain, and furthermore, dermatitis and alopecia are also common.
Currently, there is no effective treatment regimen to control the associated skin side effects caused by the administration of chemotherapeutic agents like capecitabine, and therefore new regimens are urgently needed to fill this gap.
Disclosure of Invention
Aiming at the technical current situation that no effective treatment scheme is available in the prior art for controlling the related skin side effect caused by the administration of the chemotherapeutic drugs, the invention provides the application of the nobiletin in the preparation of the drugs for preventing or treating the skin tissue diseases or symptoms related to the administration of the chemotherapeutic drugs.
The present application relates to the use of nobiletin in the manufacture of a medicament for the prevention or treatment of a skin tissue disease or disorder associated with the administration of chemotherapeutic agents including capecitabine. Specifically, the application provides an application of nobiletin in preparing a medicament for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicaments. By the application method disclosed in the application, the nobiletin can be used for preventing or treating skin tissue diseases or symptoms related to the administration of the chemotherapeutic drug in a subject, and the use of the nobiletin can effectively control the side effects of the skin caused by the chemotherapeutic drug.
The purpose of the invention can be realized by the following technical scheme:
the invention provides an application of nobiletin in preparing a medicament for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicaments.
In some embodiments of the invention, the chemotherapeutic agent is a drug for treating cancer.
In some embodiments of the invention, the chemotherapeutic agent is selected from capecitabine or a prodrug of capecitabine, 5-fluorouracil.
In some embodiments of the invention, the skin tissue disease or condition is a skin tissue disease or condition caused by administration of the chemotherapeutic agent.
In some embodiments of the invention, the skin tissue disease or disorder comprises a rash associated with administration of a chemotherapeutic agent, a hand-foot syndrome associated with administration of a chemotherapeutic agent, an itch associated with administration of a chemotherapeutic agent, a erythema associated with administration of a chemotherapeutic agent, a dry skin associated with administration of a chemotherapeutic agent, a hair loss associated with administration of a chemotherapeutic agent, a paronychia associated with administration of a chemotherapeutic agent, a pigmentation disorder associated with administration of a chemotherapeutic agent.
In some embodiments of the invention, further, the skin tissue disease or disorder is selected from hand-foot syndrome associated with administration of a chemotherapeutic agent.
In some embodiments of the invention, further, the skin tissue disease or disorder comprises a rash associated with capecitabine administration, hand-foot syndrome associated with capecitabine administration, pruritus associated with capecitabine administration, erythema associated with capecitabine administration, xerosis of skin associated with capecitabine administration, alopecia associated with capecitabine administration, paronychia associated with capecitabine administration, a pigmentation disorder associated with capecitabine administration.
In some embodiments of the invention, further, the skin tissue disease or disorder is selected from hand-foot syndrome associated with the administration of capecitabine.
In some embodiments of the invention, the disease or disorder associated with administration of capecitabine is by grade 1 or more, grade 2 or more, grade 3 or more, grade 4 or more, and/or grade 5 in NCI-CTCAE V5.0.
In some embodiments of the invention, the medicament for preventing or treating a skin tissue disease or condition associated with administration of a chemotherapeutic agent is prepared as a medicament suitable for topical or oral administration.
In some embodiments of the present invention, the medicament for preventing or treating a skin tissue disease or condition associated with administration of a chemotherapeutic agent is further prepared as an orally administered formulation suitable for oral administration.
Oral formulations include, but are not limited to, capsules, sachets, pills, tablets, lozenges (a base for taste, usually sucrose and acacia or tragacanth), powders, granules, aqueous or non-aqueous solutions or suspensions, water-in-oil or oil-in-water emulsions, elixirs or syrups, troches (suitably in an inert base such as gelatin, glycerin, sucrose or acacia), and/or mouthwashes and the like.
In some embodiments of the present invention, further, the medicament for preventing or treating a skin tissue disease or disorder associated with administration of a chemotherapeutic agent is prepared as a cream, emulsion, gel, oil, ointment, spray, foam, liposomal formulation, liniment, lotion, aerosol, and/or transdermal agent absorbed through the skin.
In some embodiments of the invention, the concentration of the nobiletin in the drug is 0.0001% (w/w) to 50% (w/w).
The invention also provides a method comprising administering nobiletin to a subject, wherein the subject has been, is being and/or will be administered a chemotherapeutic drug (particularly capecitabine) and is suffering from or susceptible to a skin tissue disease or disorder associated with administration of the chemotherapeutic drug (particularly capecitabine).
The invention also provides a method for preventing or treating a disease or disorder, comprising administering nobiletin to a subject susceptible to or suffering from a skin tissue disease or disorder associated with administration of a chemotherapeutic drug (particularly capecitabine), wherein the subject has been, is being, and/or will be administered a chemotherapeutic drug (particularly capecitabine).
Compared with the prior art, the invention provides the application of the nobiletin in preparing the medicine for preventing or treating the skin tissue diseases or symptoms related to the administration of the chemotherapeutic medicine. By the application method disclosed in the application, the nobiletin can be used for preventing or treating skin tissue diseases or symptoms related to the administration of the chemotherapeutic drug in a subject, and the use of the nobiletin can effectively control the side effects of the skin caused by the chemotherapeutic drug. The research of the invention finds that, at the cellular level, the nobiletin can relieve the negative effect of the prodrug 5-fluorouracil of capecitabine on cell proliferation. On the animal level, the nobiletin can obviously prevent the capecitabine induced hand-foot syndrome of rats.
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FIG. 1 Effect of nobiletin on alleviating the proliferative toxicity of 5-fluorouracil on HaCaT cells;
FIG. 2 is a photograph of rat hand-foot syndrome induced by capecitabine;
FIG. 3 is a photograph of rat paw with a Chuanchengsu gel-coated group;
FIG. 4 photograph of rat paw with blank gel applied.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments.
The invention achieves the purpose of relieving the skin toxicity of capecitabine by applying nobiletin. At the cellular level, nobiletin can alleviate the negative effects of capecitabine prodrug 5-fluorouracil on cell proliferation. On the animal level, the nobiletin can obviously prevent the capecitabine induced hand-foot syndrome of rats.
In the results of the examples of the present application, denotes P < 0.01; denotes P < 0.05; denotes P <0.001, using t-test statistical test.
Example 1 Effect of nobiletin on relieving the proliferative toxicity of 5-fluorouracil on HaCaT cells
Digesting the cultured skin cells HaCaT, counting, inoculating into a 96-well plate, and planting 5000-10000 cells in each well. After 24h of incubation, each well was divided into a blank solvent control group, a 5-FU group, and a 5-FU + nobiletin group. The final concentration is shown in figure 1. After culturing for another 48 hours, the Cell survival rate was measured using a Cell CountingKit-8(CCK-8) assay kit (C0037, available from Shanghai Binyan Biotech Co., Ltd.) to calculate the proliferative toxicity of 5-FU on cells and the inhibitory effect of nobiletin on the proliferative toxicity. Results were statistically analyzed and graphed using GraphPad Prism 6.0 software, t-test. Figure 1 lists the results of the experiment.
Example 2 nobiletin can alleviate capecitabine-induced hand-foot syndrome in a rat model
And (5) constructing a rat animal model. Capecitabine was administered to 6-week female SD rats by daily gavage, and several days later, hand-foot syndrome appeared in the rat paw (photographs shown in fig. 2). The difference between the left and right paws does not appear in the hands and the feet, and the degrees of the hand-foot syndrome appearing in the two paws are similar. Similar to that in humans, rats develop hand-foot syndrome in their paw following oral administration of capecitabine. The etiology of both is the same, and the symptoms are very similar. Therefore, rats are a very good animal model for simulating capecitabine-induced hand-foot syndrome.
After one week of acclimation (about 200g) of the SD rats, the rats were divided into 12 rats per group and then subjected to the gavage test. Capecitabine was dissolved in a mixed solution of castor oil and ethanol at a ratio of 1:1, diluted three times with PBS buffer solution, and administered at a dose of 1mL/100g per mouse as shown in table 1. After the stomach is perfused, fixing the rats by using a fixing cylinder, smearing the gel of the nobiletin on the double hindpaws (about 1cm by 3cm) of the rats in the drug-coated group, and smearing blank gel (as blank control) on the blank group; after about 4 hours of drug application, the rats were released, and the drug residues were wiped off with clear water and returned to the mouse cage. The gavage frequency of capecitabine is shown in table 1, and the nobiletin gel is applied with the gavage every day. The gavage and smearing tests were repeated daily until a clear hand-foot syndrome appeared in the blank group, at which time the number of rats with the skin of the paw of the smearing group kept normal or with symptoms significantly less than the hand-foot syndrome in the blank group was calculated as the number of rats that effectively inhibited the hand-foot syndrome.
TABLE 1 Effect of nobiletin on alleviating capecitabine-induced hand-foot syndrome in rat model
Table 1 and fig. 3 to 4 list the corresponding experimental results (wherein, the numerical value in the column of control rate ═ hand-foot syndrome demolding rate in blank group — hand-foot syndrome demolding rate in drug-coated group). The results show that the nobiletin can relieve the hand-foot syndrome to a certain extent.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. Use of nobiletin in preparing medicine for preventing or treating skin tissue diseases or disorders related to administration of chemotherapeutic medicine is provided.
2. The use of nobiletin according to claim 1 in the preparation of a medicament for the prevention or treatment of a skin tissue disease or disorder associated with the administration of a chemotherapeutic agent, wherein the chemotherapeutic agent is a medicament for the treatment of cancer.
3. The use of nobiletin in the preparation of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent according to claim 1, wherein the chemotherapeutic agent is capecitabine or a prodrug of capecitabine, 5-fluorouracil.
4. The use of nobiletin in the preparation of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent according to claim 1, wherein the skin tissue disease or condition is a skin tissue disease or condition caused by the administration of the chemotherapeutic agent.
5. The use of nobiletin in the manufacture of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent, according to claim 1, wherein the skin tissue disease or condition comprises a skin rash associated with the administration of a chemotherapeutic agent, hand-foot syndrome associated with the administration of a chemotherapeutic agent, itch associated with the administration of a chemotherapeutic agent, erythema associated with the administration of a chemotherapeutic agent, dry skin associated with the administration of a chemotherapeutic agent, alopecia associated with the administration of a chemotherapeutic agent, paronychia associated with the administration of a chemotherapeutic agent, pigmentation disorders associated with the administration of a chemotherapeutic agent.
6. The use of nobiletin in the manufacture of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent, according to claim 1, wherein the skin tissue disease or condition comprises a rash associated with the administration of capecitabine, hand-foot syndrome associated with the administration of capecitabine, itch associated with the administration of capecitabine, erythema associated with the administration of capecitabine, skin dryness associated with the administration of capecitabine, hair loss associated with the administration of capecitabine, paronychia associated with the administration of capecitabine, a pigmentation disorder associated with the administration of capecitabine.
7. Use of nobiletin in the manufacture of a medicament for the prevention or treatment of a skin tissue disease or condition associated with administration of a chemotherapeutic agent according to claim 1 wherein the severity of the disease or condition associated with administration of capecitabine is according to NCI-CTCAE V5.0 grade 1 or higher, grade 2 or higher, grade 3 or higher, grade 4 or higher, and/or grade 5.
8. The use of nobiletin in the preparation of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent according to claim 1, wherein the medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent is prepared as a medicament suitable for topical or oral administration.
9. The use of nobiletin in the manufacture of a medicament for the prevention or treatment of a skin tissue disorder or disease associated with the administration of a chemotherapeutic agent according to claim 8 wherein the oral formulation suitable for oral administration is selected from one or more of capsules, sachets, pills, tablets, lozenges, powders, granules, aqueous or non-aqueous solutions or suspensions, water-in-oil or oil-in-water emulsions, elixirs or syrups, lozenges, candies or mouthwashes;
the medicament suitable for external use is prepared into cream, emulsion, gel, oil, ointment, spray, foam, liposome preparation, liniment, lotion, aerosol and/or transdermal agent absorbed through skin.
10. The use of nobiletin in the preparation of a medicament for the prevention or treatment of a skin tissue disease or condition associated with the administration of a chemotherapeutic agent according to claim 1, wherein the concentration of nobiletin in the medicament is from 0.0001% (w/w) to 50% (w/w).
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| CN202110458778.7A CN113116884A (en) | 2021-04-27 | 2021-04-27 | Application of nobiletin in preparation of medicine for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicine |
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| CN202110458778.7A CN113116884A (en) | 2021-04-27 | 2021-04-27 | Application of nobiletin in preparation of medicine for preventing or treating skin tissue diseases or symptoms related to administration of chemotherapeutic medicine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114404368A (en) * | 2022-01-29 | 2022-04-29 | 广州医科大学 | Polymethoxyflavone liposome and preparation method thereof |
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| KR101651833B1 (en) * | 2015-07-17 | 2016-09-19 | 명지대학교 산학협력단 | Composition for preventing hair loss or promoting hair growth comprising extract of citrus preicarp |
| US20190046498A1 (en) * | 2017-08-11 | 2019-02-14 | Huanggang normal university | Method for treating melanoma |
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2021
- 2021-04-27 CN CN202110458778.7A patent/CN113116884A/en active Pending
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| CN103340962A (en) * | 2013-07-01 | 2013-10-09 | 石强 | Natural pharmaceutical composition, and preparation method and application thereof |
| KR101651833B1 (en) * | 2015-07-17 | 2016-09-19 | 명지대학교 산학협력단 | Composition for preventing hair loss or promoting hair growth comprising extract of citrus preicarp |
| US20190046498A1 (en) * | 2017-08-11 | 2019-02-14 | Huanggang normal university | Method for treating melanoma |
| CN112843146A (en) * | 2021-03-24 | 2021-05-28 | 中国药科大学 | New use of Chinese patent medicine sanhuang ointment |
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| HYO JUNG KIM: "Nobiletin, a Polymethoxy Flavonoid, Reduced Endothelin-1 Plus SCF-Induced Pigmentation in Human Melanocytes", 《PHOTOCHEMISTRY AND PHOTOBIOLOGY》 * |
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| 杨笛: "川陈皮素治疗皮肤疾病的研究进展", 《华西药学杂志》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114404368A (en) * | 2022-01-29 | 2022-04-29 | 广州医科大学 | Polymethoxyflavone liposome and preparation method thereof |
| CN114404368B (en) * | 2022-01-29 | 2023-02-03 | 广州医科大学 | Polymethoxyflavone liposome and preparation method thereof |
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