# US 12,178,792 B2 · Pharmaceutical composition and use thereof in preparing drug for treating tumor multi-drug resistance

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- Number: US 12,178,792 B2
- Document ID: US12178792B2
- Status: Granted
- Kind: B2
- Application number: 16/980,576
- Filed: 2019-03-12
- Published: 2021-03-25
- Granted: 2024-12-31
- Earliest claimed: 2018-03-13
- Assignees: Sichuan Jiuzhang Biological Science and Technology Co., Ltd.
- Applicants: Sichuan Jiuzhang Biological Science and Technology Co., Ltd.
- Inventors: Jie Zhang; Xiaoguang Chen; Huarong Yang; Wang Huang
- Web page: https://patentgrep.com/patent/US12178792B2

## CPC

- A61K 31/216: of acids having aromatic rings, e.g. benactizyne, clofibrate
- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

A pharmaceutical composition includes chlorogenic acid and coumaroylquinic acid. It can be used for preparing a reversing agent for tumor multi-drug resistance and a PD-1/PD-L1 inhibitor. The combined use of chlorogenic acid and coumaroylquinic acid exhibits a synergistic effect, effectuating a good reversing effect on the drug resistance of a tumor cell strain that produces multi-drug resistance for chemotherapeutic drugs and immunotherapeutic drugs, which may effectively inhibit PD-1/PD-L1 expression in drug-resistant B16 melanoma and drug-resistant Lewis lung cancer mice transplantation tumor tissue, and may effectively proliferate CD4+T and CD8+T cells in drug-resistant B16 melanoma mice and Lewis lung cancer mice.

## Claims

### Claim 1

A method for treating multidrug resistance to a tumor, comprising administering to a subject in need thereof a reversal agent, wherein the reversal agent comprises chlorogenic acid and a coumaroylquinic acid at a mass ratio of chlorogenic acid to coumaroylquinic acid of 100:0.01 to 100:0.5, wherein said tumor is melanoma or lung cancer, and is resistant to dacarbazine, gemcitabine, or nivolumab.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the mass ratio of chlorogenic acid to coumaroylquinic acid is 100:0.01 to 100:0.1.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the mass ratio of chlorogenic acid to coumaroylquinic acid is 100:0.05.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the reversal agent further comprises a pharmaceutically acceptable excipient.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the reversal agent is an oral or injectable preparation.

### Claim 6

A method for treating a tumor, comprising:
administering to a subject in need thereof an antitumor drug and a reversal agent,
wherein the antitumor drug is dacarbazine, gemcitabine, or nivolumab,
wherein the reversal agent comprises chlorogenic acid and a coumaroylquinic acid at a mass ratio of chlorogenic acid to coumaroylquinic acid of 100:0.01 to 100:0.5, and
wherein said tumor is melanoma or lung cancer.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the mass ratio of chlorogenic acid to coumaroylquinic acid is 100:0.01 to 100:0.1.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the mass ratio of chlorogenic acid to coumaroylquinic acid is 100:0.05.

### Claim 9 (depends on 6)

The method according to claim 6, wherein the reversal agent further comprises a pharmaceutically acceptable excipient.

### Claim 10 (depends on 6)

The method according to claim 6, wherein the reversal agent is an oral or injectable preparation.

### Claim 11 (depends on 6)

The method according to claim 6, wherein the reversal agent and the antitumor drug are administered separately.