CN110179976A - Combined pharmaceutical formulation for treating cancer - Google Patents
Combined pharmaceutical formulation for treating cancer Download PDFInfo
- Publication number
- CN110179976A CN110179976A CN201910427154.1A CN201910427154A CN110179976A CN 110179976 A CN110179976 A CN 110179976A CN 201910427154 A CN201910427154 A CN 201910427154A CN 110179976 A CN110179976 A CN 110179976A
- Authority
- CN
- China
- Prior art keywords
- antibody
- cancer
- pharmaceutical formulation
- pirfenidone
- combined pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a kind of combined pharmaceutical formulation for treating cancer, and the composition of medicine includes a effective amount of PD-L1 antibody and pirfenidone；The effective percentage of immunization therapy can be improved in pharmaceutical preparation of the present invention, solves the problems, such as that existing PD-L1 antibody list medicine tumor killing effect is bad, and more cancer patients is allowed to be benefited.
Description
Technical field
The present invention relates to treating cancer fields, and in particular to a kind of combined pharmaceutical formulation for treating cancer.
Background technique
Apoptosis albumen -1 (programmed death-1, PD-1) and its ligand (PD-L1) inhibitor are
Immunologic test point monoclonal antibody medicine, has with the kinds cancers patients such as melanoma, non-small cell lung cancer and urothelial cancer
Good curative effect.It not only changes the treatment mode of malignant tumour, also extends total life span of patient.In tumour micro-loop
In border, PD-L1 antibody can target the combination of competition PD-L1 and PD-1, release t cell activation and inhibit, make antigen presenting cell more
Antigen presentation to T cell and is efficiently made into T cell differentiation activation.
However, effective percentage of the immunization therapy with cancer patient is only 20% or so, it is current for how improving effective percentage
Urgent problem to be solved.Have a large number of studies show that, the collagen stroma in tumor microenvironment can form fibrin barriers, prevent immune thin
The infiltration of born of the same parents makes patient generate primary or secondary resistance to immunization therapy.
Therefore, inhibit collagen to be formed, reduce fiber deposition to may be a kind of raising immunization therapy efficient way.
Summary of the invention
The present invention problem not ideal enough for existing PD-L1 antibody list medicine cancer resistant effect provides a kind of for treating
The combined pharmaceutical formulation of cancer, the pharmaceutical preparation use effective dose PD-L1 antibody (- 1 antibody of apoptosis albumen)
The remarkable effect in terms of inhibiting tumour growth is used in combination with pirfenidone, has combined immunologic test point inhibitor and anti-fiber
Chemical drug object can solve the problems, such as that some patientss react bad to immunologic test point inhibitor.
To achieve the above object, a kind of combined pharmaceutical formulation for treating cancer designed by the present invention, the combination medicine
Object includes a effective amount of PD-L1 antibody and pirfenidone.
Pirfenidone is a kind of new pyridine compounds with wide spectrum anti-fibrosis effect, entitled 5 methyl 1 of chemistry
Phenyl 2- (1 H) pyridone is a kind of white or light yellow crystalline powder, can prevent and reverse fibrosis and scar
It is formed.It was listed by the wild justice of Japanese salt in 2008, has obtained U.S. Food and Drug Administration's approval, be first and pass through weight
Multiple, random, placebo III clinical trial phase proves the drug for having certain curative effect to idiopathic pulmonary fibrosis (IPF).
Pirfenidone can inhibit fibroblast proliferation in the present invention, and fibroblast is prevented to convert to flesh at fiber,
It reduces and promotees the expression of fiber correlation factor.Therefore, being used to enhance the curative effect of immunologic test point inhibitor for pirfenidone auxiliary is one
A effective method.
Further, in the pharmaceutical preparation, the content of pirfenidone be 10-50mg/ml, PD-L1 antibody be 0.1~
0.3mg/ml。
Still further, the quality proportioning of PD-L1 antibody and pirfenidone is 1:100~300 in the pharmaceutical preparation.
Still further, the content of the pirfenidone is that 20-30mg/ml, PD-L1 antibody are in the pharmaceutical preparation
0.1mg/ml。
Still further, the content of the pirfenidone is that 30mg/ml, PD-L1 antibody are in the pharmaceutical preparation
0.1mg/ml。
Still further, the pharmaceutical preparation further includes pharmaceutically acceptable auxiliary material.
Still further, the auxiliary material is physiological saline, glucose solution, vitamin C, sorbierite, mannitol, xylose
Any one in alcohol, fructose, amino acid, meglumine, dextrin, magnesium stearate and sucrose or two kinds.
Still further, the cancer is lung cancer, colon cancer.
Beneficial effects of the present invention:
The effective percentage of immunization therapy can be improved in pharmaceutical preparation of the present invention, solves existing PD-L1 antibody list medicine suppression
The bad problem of tumor effect allows more cancer patients to be benefited.
Detailed description of the invention
Fig. 1 is mouse tumor volume growth curve figure (* indicates P < 0.05)；
In figure, left figure is mice lung cancer model growth curve chart；Right figure is mouse junction cancer model growth curve chart；
Fig. 2 is mouse survival curve graph；
In figure, left figure is mice lung cancer model survivorship curve figure；Right figure is mouse junction cancer model survivorship curve figure；
Fig. 3 is with CD45+ immunocyte infiltration degree in Flow cytometry tumor tissues；
In figure, Fig. 3 a is the streaming schematic diagram that CD45+ immunocyte accounts for live cell fraction；Fig. 3 b is CD45+ immunocyte
Account for the statistical chart of live cell fraction；
Fig. 4 is with CD8+ immunocyte infiltration degree in Flow cytometry tumor tissues；
In figure, Fig. 4 a is the streaming schematic diagram of the total T cell ratio of CD8+T cell Zhan；Fig. 4 b is that the total T of CD8+T cell Zhan is thin
The statistical chart of born of the same parents' ratio；
Specific embodiment
The present invention is described in further detail combined with specific embodiments below, so as to those skilled in the art understand that.
Embodiment 1: inhibit the effect of tumour growth in pirfenidone combined PD-L1 antibody body
Test material therefor: normal 6-8 week old female C57BL/6 mouse is several, the strain of MC38 mouse colonic cell, LLC are small
Mouse lung cancer cell line, pirfenidone, PD-L1 antibody, 1640 culture mediums, 10% fetal calf serum, sterile PBS；
Mouse experiment process is as follows:
1) the right back hair of mouse is shaved with shave, 1*10 is subcutaneously injected6A MC38 tumour cell；
2) region tumors volume 100cm to be seeded3When, mouse is randomly divided into 4 groups, control group (control, abdominal cavity note
Penetrate sterile PBS), pirfenidone list medicine group (PFD, be injected intraperitoneally pirfenidone 300mg/kg), PD-L1 antibody list medicine group (α PD-
L1, be injected intraperitoneally PD-L1 antibody 2mg/kg), joint group (PFD+ α PD-L1, be injected intraperitoneally hybrid medicine, contain pirfenidone
300mg/kg, PD-L1 antibody 2mg/kg).It is administered once a day, until mouse leads to death or tumour because tumor load is overweight
Volume is more than 2000cm3；
3) a mouse tumor volume is measured every three days, when gross tumor volume is more than 2000cm3When, put to death mouse.
Experimental result:
1, PD-L1 antibody list medicine group Tumor growth inhibition acts on unobvious (Fig. 1)；
2, pirfenidone list medicine can inhibit tumour growth, but mouse has no that obvious existence benefits (Fig. 1~2)；
3, two medicine joint group mice tumors grews inhibit obvious, and more single medicine group effect is good, reaches statistical significance；Joint group
The mouse survival time is obviously prolonged (Fig. 1~2).
Embodiment 2: the influence of pirfenidone combined PD-L1 Antibody on Mouse tumor microenvironment
Test material therefor: normal 6-8 week old female C57BL/6 mouse is several, MC38 cell strain, pirfenidone, PD-L1 are anti-
Body, 1640 culture mediums, 10% fetal calf serum, sterile PBS, IV Collagenase Type, fluorescent marker antibody (Cy5.5 anti-mouse
CD4, APC anti-mouse CD8, FITC anti-mouse CD45), BD LSRII streaming instrument；
Experiment flow:
1) it is inoculated with oncocyte, dosing step is same as Example 1；
2) it is administered the tenth day, puts to death mouse, go out subcutaneous tumors, knurl is subtracted into fritter, be digested to list with IV Collagenase Type
Cell suspension；
3) single cell suspension is divided into several tubules, be centrifuged, abandon supernatant, the antibody mixing of fluorescent marker is added into precipitating
Liquid, 4 degree are incubated for 30 minutes；
4) antibody is washed away with PBS, cell is resuspended with 500 microlitres of PBS, is detected with flow cytometer, it is soft with Flowjo
Part analyzes result.
Experimental result:
1, Fig. 3 A is shown, two medicine joint groups compare control, single medicine group, immunocyte (CD45+ leucocyte) increasing proportion；Figure
3B shows immunocyte increasing proportion in joint group per unit weight tumour；-
2, Fig. 4 A is shown, two medicine joint groups compare control group, single medicine group, cytotoxic T cell (CD8+ lymphocyte) ratio
Example increases；Fig. 4 B shows T cell increasing proportion in joint group per unit weight tumour；
Therefore, the immune microenvironment of tumour can be changed in drug combination, enhances the anti-tumor effect of body itself, to reach
Inhibit the effect of tumour growth.
Embodiment 3
Combined pharmaceutical formulation 1 for treating cancer, wherein the content of pirfenidone is that 10mg/ml, PD-L1 antibody are
0.3mg/ml, remaining is physiological saline.
Embodiment 4
Combined pharmaceutical formulation 2 for treating cancer, wherein the content of pirfenidone is that 30mg/ml, PD-L1 antibody are
0.1mg/ml, remaining is physiological saline.
Embodiment 5
Combined pharmaceutical formulation 3 for treating cancer, wherein the content of pirfenidone is that 10mg/ml, PD-L1 antibody are
0.1mg/ml, remaining is physiological saline.
Embodiment 6
Combined pharmaceutical formulation 4 for treating cancer, wherein in the pharmaceutical preparation, the content of pirfenidone is 20mg/
Ml, PD-L1 antibody are 0.1mg/ml, remaining is physiological saline.
Embodiment 7
Combined pharmaceutical formulation 5 for treating cancer, wherein in the pharmaceutical preparation, the content of pirfenidone is 50mg/
Ml, PD-L1 antibody are 0.1mg/ml, remaining is physiological saline.
Embodiment 8
Combined pharmaceutical formulation 6 for treating cancer, wherein in the pharmaceutical preparation, the content of pirfenidone is 30mg/
Ml, PD-L1 antibody are 0.1mg/ml, remaining is physiological saline.
Other unspecified parts are the prior art.Although above-described embodiment is made that the present invention and retouches in detail
State, but it is only a part of the embodiment of the present invention, rather than whole embodiments, people can also according to the present embodiment without
Other embodiments are obtained under the premise of creativeness, these embodiments belong to the scope of the present invention.
Claims (8)
1. a kind of combined pharmaceutical formulation for treating cancer, it is characterised in that: the composition of medicine includes a effective amount of PD-L1
Antibody and pirfenidone.
2. being used for the combined pharmaceutical formulation of anticancer according to claim 1, it is characterised in that: in the pharmaceutical preparation, pyrrole is non-
The content of Buddhist nun's ketone is that 10-50mg/ml, PD-L1 antibody are 0.1~0.3mg/ml.
3. being used for the combined pharmaceutical formulation for the treatment of cancer according to claim 2, it is characterised in that: in the pharmaceutical preparation,
The quality proportioning of PD-L1 antibody and pirfenidone is 1:100~300.
4. being used for the combined pharmaceutical formulation for the treatment of cancer according to claim 3, it is characterised in that: in the pharmaceutical preparation,
The content of pirfenidone is that 20-30mg/ml, PD-L1 antibody are 0.1mg/ml.
5. being used for the combined pharmaceutical formulation for the treatment of cancer according to claim 5, it is characterised in that: in the pharmaceutical preparation,
In the pharmaceutical preparation, the content of the pirfenidone is that 30mg/ml, PD-L1 antibody are 0.1mg/ml.
6. being used for the combined pharmaceutical formulation for the treatment of cancer described according to claim 1~any one of 5, it is characterised in that: institute
Stating pharmaceutical preparation further includes pharmaceutically acceptable auxiliary material.
7. being used for the combined pharmaceutical formulation for the treatment of cancer according to claim 6, it is characterised in that: the auxiliary material is physiology salt
Water, glucose solution, vitamin C, sorbierite, mannitol, xylitol, fructose, amino acid, meglumine, dextrin, magnesium stearate and
Any one in sucrose or two kinds.
8. according to claim 1 be used for treating cancer combined pharmaceutical formulation, it is characterised in that: the cancer be lung cancer or
Colon cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910427154.1A CN110179976A (en) | 2019-05-22 | 2019-05-22 | Combined pharmaceutical formulation for treating cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910427154.1A CN110179976A (en) | 2019-05-22 | 2019-05-22 | Combined pharmaceutical formulation for treating cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110179976A true CN110179976A (en) | 2019-08-30 |
Family
ID=67717225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910427154.1A Pending CN110179976A (en) | 2019-05-22 | 2019-05-22 | Combined pharmaceutical formulation for treating cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110179976A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6022538A (en) * | 1995-06-06 | 2000-02-08 | The Wistar Institute Of Anatomy And Biology | Method of treating malignancies |
| CN109312408A (en) * | 2016-05-17 | 2019-02-05 | 豪夫迈·罗氏有限公司 | For diagnosing and signing for matrix gene used in immunotherapy |
-
2019
- 2019-05-22 CN CN201910427154.1A patent/CN110179976A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6022538A (en) * | 1995-06-06 | 2000-02-08 | The Wistar Institute Of Anatomy And Biology | Method of treating malignancies |
| CN109312408A (en) * | 2016-05-17 | 2019-02-05 | 豪夫迈·罗氏有限公司 | For diagnosing and signing for matrix gene used in immunotherapy |
Non-Patent Citations (1)
| Title |
|---|
| 王海洋、俞晓晴: "免疫检查点抑制剂一线治疗晚期NSCLC的", 《中国肺癌杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111065411B (en) | Use of PD-1 antibody and VEGFR inhibitor for combined treatment of small cell lung cancer | |
| CN101014365B (en) | Combination treatment for non-hematologic malignancies using an anti-igf-1r antibody | |
| JP5178663B2 (en) | Combination therapy using an anti-angiogenic agent and TNFα | |
| KR102002653B1 (en) | Composition comprising aflibercept, folinic acid, 5-fluorouracil(5-fu) and irinotecan(folfiri) | |
| EP0806963B1 (en) | Carcinoma treatment | |
| KR20170015460A (en) | Methods of cancer treatment with antagonists against pd-1 and pd-l1 in combination with radiation therapy | |
| CN108136022A (en) | Use B-RAF inhibitor and the method for immunologic test point inhibitor for treating cancer | |
| AU2002316855A1 (en) | Combination therapy using anti-angiogenic agents and TNFalpha | |
| CN110494152A (en) | Short TRAIL antibody and application method | |
| FI114011B (en) | Use of Immunoglobulin for Intravenous Use in the Preparation of a Pharmaceutical Composition for the Treatment of Cancer Diseases | |
| CN101920015A (en) | Pharmaceutical composition for cancer treatment | |
| CN111920948B (en) | Pharmaceutical composition comprising immune cells for treating cancer | |
| CN110179976A (en) | Combined pharmaceutical formulation for treating cancer | |
| TW202114647A (en) | Small molecule inhibitor for treating cancer in tumor subject with high interstitial fluid pressure | |
| US20230270861A1 (en) | Inhibitors of the Artemin Pathway for Treatment of Cancer | |
| CN111419832B (en) | Pharmaceutical composition and application thereof in preparation of tumor treatment drugs | |
| AU2020338366B2 (en) | Phenothiazines and their derivatives for use as a medicament | |
| CN112194723B (en) | Application of immune cells in treating cancer | |
| AU2020101967A4 (en) | Combined pharmaceutical preparation for treating cancer | |
| WO2021182572A1 (en) | Medicament for treatment and/or prevention of cancer | |
| CN117224689B (en) | Use of a combination of an anti-HER 2 antibody and a chemotherapeutic agent for the treatment of gastric cancer | |
| Saurez-Martínez et al. | Nimotuzumab, inmunoterapia eficaz para el tratamiento de tumores epiteliales malignos | |
| CN112168971B (en) | Application of anti-VEGF antibody and PDGF/PDGFR inhibitor in preparation of medicines for treating FGF 2-expressing tumors | |
| KR20190091299A (en) | Pharmaceutical compositions for use in the treatment of cancer | |
| CN109674788B (en) | Application of carboxyamidotriazole and IDO1 inhibitor combination in resisting tumors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190830 |