CN117379459A - Composition for treating melanoma - Google Patents

Composition for treating melanoma Download PDF

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Publication number
CN117379459A
CN117379459A CN202310811028.2A CN202310811028A CN117379459A CN 117379459 A CN117379459 A CN 117379459A CN 202310811028 A CN202310811028 A CN 202310811028A CN 117379459 A CN117379459 A CN 117379459A
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Prior art keywords
dendritic cells
composition
melanoma
fangchinoline
treating melanoma
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CN202310811028.2A
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Chinese (zh)
Inventor
王坤
肖建勇
刘芳
胡珊
廖媛
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Guangzhou University of Traditional Chinese Medicine
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Guangzhou University of Traditional Chinese Medicine
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Priority to CN202310811028.2A priority Critical patent/CN117379459A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4748Quinolines; Isoquinolines forming part of bridged ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/15Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
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  • Hematology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention discloses a composition for treating melanoma, and belongs to the technical field of medicines; the composition for treating melanoma provided by the invention comprises tetrandrine and dendritic cells. According to the composition for treating melanoma, the fangchinoline and the dendritic cells are subjected to synergistic action, so that on one hand, the fangchinoline can enhance the antigen cross presentation function of the dendritic cells, activate the immune system to clear tumors, realize autoimmune treatment, and on the other hand, the dendritic cells can further enhance the anti-tumor effect of the fangchinoline; thereby obtaining excellent melanoma treatment effect; the composition for treating melanoma has low toxic and side effects, can be used for preparing a pharmaceutical preparation, can be used in combination with other common medicines or routes for treating melanoma, improves the treatment effect and prolongs the survival time of patients.

Description

Composition for treating melanoma
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a composition for treating melanoma.
Background
Melanoma is a skin tumor with extremely high malignancy, and the morbidity and mortality rate rise year by year, which causes serious threat to human life health. Melanoma is often found in the skin, and can also occur in various parts or tissues such as mucous membranes, uvea oculi, pia mater, etc. Although there are treatment schemes aiming at melanoma at present, although melanoma at different positions has certain similarity, the treatment schemes cannot be used equally; for example, conjunctival melanoma and melanoma are malignant tumors, but the occurrence positions of the malignant tumors are different, the conjunctival melanoma is malignant tumor occurring on conjunctiva, and the melanoma is generally malignant tumor occurring on skin, mucous membrane, fundus and the like, and the treatment scheme cannot be simply migrated due to the different occurrence positions.
Immune surveillance is an important way for eliminating cancerous cells in the human body, and when the immune surveillance function is impaired, malignant transformation of melanocytes cannot be recognized and eliminated in time, resulting in immune escape and occurrence of melanoma. Dendritic Cells (DCs) as the strongest antigen presenting cells have a key role in human tumor immune monitoring; the absence of cross-presentation function of DC antigens is a significant cause of immune escape of tumor cells. Therefore, it is of great importance to find compounds that enhance the cross-presentation function of DC antigens.
Disclosure of Invention
The present invention aims to overcome the above-mentioned disadvantages of the prior art and to provide a composition for treating melanoma.
To achieve the above object, in a first aspect of the present invention, there is provided a composition for treating melanoma, the composition comprising fangchinoline and dendritic cells.
According to the composition for treating melanoma, provided by the invention, the synergistic effect is achieved through the fangchinoline and the dendritic cells (DC cells), so that an excellent melanoma treatment effect is obtained, and the obtained composition can obviously reduce the volume and weight of tumors in animal experiments; specifically, the fangchinoline and the dendritic cells act synergistically, on one hand, the fangchinoline can enhance the antigen cross-presenting function of the dendritic cells, activate the immune system to clear tumors, realize autoimmune treatment, avoid immune related side effects possibly caused by exogenous immunotherapy, and on the other hand, the dendritic cells can further enhance the anti-melanoma effect of the fangchinoline; meanwhile, the fangchinoline is a natural compound, and the dendritic cells are immune cells, so that the fangchinoline and the fangchinoline have good biocompatibility and lower toxic and side effects.
As a preferred embodiment of the composition of the present invention, the ratio of dendritic cells to fangchinoline is (1X 10) 6 -1×10 7 ) The following steps: (5-15) mg.
Preferably, the ratio of dendritic cells to fangchinoline in the composition is (2×10) 6 -5×10 6 ) The following steps: (8-12) mg.
More preferably, the ratio of dendritic cells to fangchinoline in the composition is 2.5X10 6 The following steps: 10mg.
The inventor researches find that the ratio of the dendritic cells to the fangchinoline in the provided composition can also influence the performance of the product, and when the ratio of the dendritic cells to the fangchinoline is within the range given by the invention, the dendritic cells and the fangchinoline can exert more excellent synergistic effect, and the obtained product has more excellent treatment effect on melanoma.
As a preferred embodiment of the composition of the present invention, the dendritic cells are monocyte-derived dendritic cells.
The inventor researches and discovers that when dendritic cells from different sources are selected, the effect of the obtained product is better.
As a preferred embodiment of the composition of the present invention, the melanoma is skin melanoma.
Although melanoma at different positions has certain similarity, the treatment modes also have differences due to different positions, and the inventor researches show that the composition provided by the invention has better treatment effect on skin melanoma.
In a second aspect of the invention, the invention provides a pharmaceutical formulation for the treatment of melanoma, the pharmaceutical formulation comprising fangchin alkali and dendritic cells.
As a preferred embodiment of the pharmaceutical preparation of the present invention, the dendritic cells are monocyte-derived dendritic cells.
As a preferred embodiment of the pharmaceutical formulation according to the invention, the melanoma is cutaneous melanoma.
As a preferred embodiment of the pharmaceutical preparation of the present invention, the dosage of fangchinoline is (5-15) mg/kg, and the dosage of dendritic cells is (1X 10) 6 -1×10 7 ) And (3) each kg.
Preferably, in the pharmaceutical preparation, the dosage of fangchinoline is (8-12) mg/kg, and the dosage of dendritic cells is (2×10) 6 -5×10 6 ) And (3) each kg.
More preferably, in the pharmaceutical preparation, the dosage of the fangchinoline is 10mg/kg, and the dosage of the dendritic cells is 2.5X10 6 And (3) each kg.
As a preferred embodiment of the pharmaceutical formulation according to the invention, the pharmaceutical formulation further comprises a pharmaceutically acceptable carrier.
As a preferred embodiment of the pharmaceutical preparation of the present invention, the pharmaceutical preparation is in the form of an injection.
In a third aspect of the invention, the invention provides a pharmaceutical composition for treating melanoma, comprising the composition for treating melanoma of the invention, and other drugs commonly used for treating melanoma.
As a preferred embodiment of the pharmaceutical composition of the present invention, the other commonly used drugs for treating melanoma include at least one of paclitaxel, cisplatin, temozolomide, dacarbazine, carboplatin, and vemurafenib.
As a preferred embodiment of the pharmaceutical composition of the present invention, the dendritic cells are monocyte-derived dendritic cells.
As a preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
In a fourth aspect of the invention, the invention provides the use of a combination of fangchinoline and dendritic cells for the preparation of a medicament for the treatment of melanoma.
As a preferred embodiment of the use according to the invention, the dendritic cells are monocyte-derived dendritic cells.
As a preferred embodiment of the use according to the invention, the melanoma is skin melanoma.
Compared with the prior art, the invention has the beneficial effects that:
according to the composition for treating melanoma, the fangchinoline and the dendritic cells are subjected to synergistic action, so that on one hand, the fangchinoline can enhance the antigen cross presentation function of the dendritic cells, activate the immune system to clear tumors, realize autoimmune treatment, and on the other hand, the dendritic cells can further enhance the anti-tumor effect of the fangchinoline; thereby obtaining excellent melanoma treatment effect; the composition for treating melanoma has low toxic and side effects, can be used for preparing a pharmaceutical preparation, can be used in combination with other common medicines or routes for treating melanoma, improves the treatment effect and prolongs the survival time of patients.
Drawings
FIG. 1 is a graph showing the effect of fangchinoline on antigen cross-presentation function in example 1;
FIG. 2 is a graph showing the comparison of the results of the tumor blocks in example 2.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
Unless otherwise specified, reagents and equipment used in the present invention are all conventionally available.
Example 1
The embodiment of the invention explores the influence of fangchinoline on antigen cross presentation function, and specifically comprises the following steps:
the experimental steps are as follows: the effect of fangchinoline (Fan) on MutuDC antigen cross presentation was flow tested using the DC cell line MutuDC. Grouping: negative, igG, ctrl, fan. Mu.M, six-well plate MutuDC plate 100 ten thousand/well, next day with Fan and OVA protein, four wells with OVA protein 100ug/mL, last group with Fan 5. Mu.M, 24H after action, on-machine detection, OVA257-264 (SIINFEKL) peptide is MHC class I molecule (H-2K in mice) b ) Restricted OVA polypeptide epitope, mutuDC cell surface H-2K b How much of the/SIINFEKL complex represents the size of the MutuDC antigen cross-presentation capacity. In this experiment we used specifically recognized H-2K b After staining, the fluorescent antibody of the SIINFEKL complex is subjected to flow detection, and the stronger the fluorescence intensity is, the stronger the MutuDC antigen cross-presentation capability is represented.
The obtained results are shown in figure 1, and the dendritic cells treated by the fangchinoline can obviously enhance the presentation of OVA proteins.
Example 2
The embodiment of the invention explores the treatment effect of tetrandrine and dendritic cells on mouse melanoma, and specifically comprises the following steps:
(1) Inoculating a C57BL/6 mouse through B16 cells (mouse melanoma cells) to construct a mouse transplantation tumor model;
(2) Mice with successfully constructed melanoma transplantation tumor models were grouped into Ctrl, DC, fan, DC +Fan groups of 8 mice each. Ctrl is a blank group, neither vaccinated with DC cells nor subjected to Fan treatment; example 1 both DC cells were seeded and Fan treated; comparative example 1 was only DC cell seeded, without Fan treatment; comparative example 2 was treated with Fan alone and was not inoculated with DC cells. Three days before DC cell inoculation, the corresponding groups of example 1 and comparative example 2 were subjected to intraperitoneal injection of corresponding doses of fangchinoline, three consecutive days, once a day, and the comparative example 1 and the blank group were injected with physiological saline at a dose of 10mg/kg at the same time; three days after continuous injection, the groups corresponding to example 1, comparative example 1 were dosed with DC cells; example 1 and comparative example 2 the daily injection of fangchinoline according to the table dose was continued until the material was obtained, the tumor volume was recorded daily on day 6, the tumor volume of each group was measured first on day 15, and then the tumor was taken out and photographed.
TABLE 1
Fanghexiline base Monocyte-derived DC cells
Blank group 0 0
Example 1 10mg/kg 2.5×10 6 Individual/kg
Comparative example 1 0 2.5×10 6 Individual/kg
Comparative example 2 10mg/kg 0
(3) Measuring tumor volume and recording every day from the 6 th day of inoculation, taking materials 15 days after inoculation, dissecting tumor, photographing and measuring tumor weight of tumor, and recording in table 2, wherein nd represents the nth day after inoculation of melanoma cells, tumor weight is the weight after 15 days of inoculation of melanoma cells, dissecting tumor, cleaning and absorbing water; the values are all average values of each group
TABLE 2
0d(mm 3 ) 6d(mm 3 ) 10d(mm 3 ) 15d(mm 3 ) Tumor weight (g)
Blank group 0 30.75 196 927 1.2539
Example 1 0 9.26 66 269 0.7348
Comparative example 1 0 25 193 967 1.4089
Comparative example 2 0 34 104 951 1.4076
As can be seen from Table 2, when the technical scheme of the invention is adopted (example 1), the growth rate of the tumor can be obviously controlled, the tumor volume after inoculation is slowly increased, and the average volume of the tumor at 15d after inoculation is 269mm 3 The average tumor weight is 0.735g, and compared with a blank group, the volume reduction amplitude is more than 70 percent, and the tumor weight reduction amplitude is more than 40 percent; it can be seen from example 1 and comparative examples 1 to 2 that the antitumor effect could not be achieved without adding fangchinoline or dendritic cells; wherein fig. 2 is a photograph of melanoma pieces in a blank group (Ctrl), example 1 (fan+dc), comparative example 1 (DC) and comparative example 2 (Fan), which were photographed 15 days later when the materials were taken. The visual observation of the figure shows that the tumor volume can be effectively reduced only under the technical scheme provided by the invention, and the excellent treatment effect is achieved.
Finally, it should be noted that the above-mentioned embodiments illustrate rather than limit the scope of the invention, and that those skilled in the art will understand that changes can be made to the technical solutions of the invention or equivalents thereof without departing from the spirit and scope of the technical solutions of the invention.

Claims (10)

1. A composition for treating melanoma, comprising fangchinoline and dendritic cells.
2. The composition of claim 1, wherein the ratio of dendritic cells to fangchinoline is (1 x 10) 6 -1×10 7 ) The following steps: (5-15) mg.
3. The composition of claim 1, wherein the dendritic cells are monocyte-derived dendritic cells.
4. The composition of claim 1, wherein the melanoma is skin melanoma.
5. A pharmaceutical formulation for treating melanoma, comprising fangchinoline and dendritic cells.
6. The pharmaceutical formulation according to claim 5, wherein the dosage of fangchinoline is (5-15) mg/kg and the dosage of dendritic cells is (1 x 10) 6 -1×10 7 ) And (3) each kg.
7. The pharmaceutical formulation of claim 5, further comprising a pharmaceutically acceptable carrier.
8. The pharmaceutical formulation of claim 5, wherein the pharmaceutical formulation is in the form of an injection.
9. A pharmaceutical composition for treating melanoma, comprising the composition for treating melanoma according to claim 1, and other drugs commonly used for treating melanoma.
10. The application of the combined drug of the tetrandrine and the dendritic cells in preparing the drugs for treating melanoma.
CN202310811028.2A 2023-07-04 2023-07-04 Composition for treating melanoma Pending CN117379459A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310811028.2A CN117379459A (en) 2023-07-04 2023-07-04 Composition for treating melanoma

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310811028.2A CN117379459A (en) 2023-07-04 2023-07-04 Composition for treating melanoma

Publications (1)

Publication Number Publication Date
CN117379459A true CN117379459A (en) 2024-01-12

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Country Status (1)

Country Link
CN (1) CN117379459A (en)

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