# US 11,439,586 B2 · Intratumour injection formulation

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,439,586 B2
- Document ID: US11439586B2
- Status: Granted
- Kind: B2
- Application number: 16/544,146
- Filed: 2019-08-19
- Published: 2020-04-16
- Granted: 2022-09-13
- Earliest claimed: 2018-10-16
- Assignees: US Nano Food & Drug, Inc
- Applicants: US Nano Food & Drug INC
- Inventors: Hing Sang Pui; Yip Shu Pui
- Web page: https://patentgrep.com/patent/US11439586B2

## CPC

- 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 31/337: having four-membered rings, e.g. taxol
- A61K 31/357: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 35/00: Antineoplastic agents
- 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

## Abstract

Formulations and uses of the formulations for treating a malignant mass in a mammal by administering an injectable formulation comprising a therapeutically effective amount of a chemotherapeutic agent dissolved or suspended in a biocompatible carrier directly into the malignant mass are disclosed. In certain preferred embodiments, the injectable formulation is a taxane (e.g. paclitaxel), a podophyllotoxin derivative (e.g., etoposide), or a camptothecin derivative (e.g., hydroxycamptothecin).

## Claims

### Claim 1

A method of treating a malignant mass in a mammal, comprising administering an injectable formulation suitable for intratumor administration directly into the malignant mass, the injectable formulation consisting of a therapeutically effective amount of a water insoluble chemotherapeutic agent selected from a taxane, a podophyllotoxin derivative, a camptothecin derivative, and mixtures thereof dissolved or suspended in a pharmaceutically acceptable biocompatible carrier comprising a medium chain triglyceride or a pharmaceutically acceptable vegetable oil, and an optional solvent which when included consists of a non-aqueous solvent, wherein the injectable formulation is a colorless and transparent stable non-aqueous solution that does not include cholesterol, a phospholipid, a protein, or surfactant.

### Claim 2 (depends on 1)

The method of claim 1, wherein the malignant mass is in a location in the mammal selected from the group consisting of brain, head, eye, nasopharynx, mouth, tongue, neck, thyroid, gastrointestinal system, liver, pancreas, gall bladder, lung, respiratory system, urogenital system, kidney, urinary bladder, breast, lymphatic system, cardiovascular system, nervous system, skin, thorax, pleural membrane, mesothelioma, lung cancer, muscular skeletal system, abdomen with primary or secondary nature.

### Claim 3 (depends on 2)

The method of claim 2, wherein the malignant mass metastasized from another organ in the mammal.

### Claim 4 (depends on 2)

The method of claim 2, wherein the injectable formulation is administered through a syringe or a needle of a fiberscope.

### Claim 5 (depends on 4)

The method of claim 4, wherein the chemotherapeutic agent is a water insoluble compound selected from the group consisting of a taxane, a podophyllotoxin derivative, or a camptothecin derivative.

### Claim 6 (depends on 5)

The method of claim 5, wherein the water insoluble compound is a taxane selected from the group consisting of paclitaxel and doxetaxel.

### Claim 7 (depends on 5)

The method of claim 5, wherein the water insoluble compound is hydroxycamptothecin.

### Claim 8 (depends on 5)

The method of claim 5, wherein the biocompatible carrier comprises a medium chain triglyceride and further includes a hydroalcoholic solvent.

### Claim 9 (depends on 1)

The method of claim 1, wherein the chemotherapeutic agent is paclitaxel and the biocompatible carrier comprises a medium chain triglyceride.

### Claim 10 (depends on 1)

The method of claim 1, wherein the malignant mass is
(i) a superficial malignant disease of skin, eye, tongue, mouth, thyroid, breast, cervix, uterus, anus, prostate, vagina, sarcoma of the bone, carcinoma of urethra, penis, testis and epididymis and the chemotherapeutic agent is injected with a syringe directly into the malignant mass without dilution; or
(ii) a cancer of the nasopharynx, and the chemotherapeutic agent is injected into the malignant mass with the syringe or needle through a nasopharyngoscope; or
(iii) a cancer of the liver, kidney and gall bladder, and the chemotherapeutic agent is injected using a syringe through skin into the malignant mass with the assistance of ultrasound, or is injected through a hole made in an abdominal wall of a patient during laparoscopic surgery into the malignant mass; or
(iv) a cancer of the ovary, oviduct, pancreas, metastasis of lymph node or direct peritoneum invasion of the abdominal cavity, lymphoma of the abdomen, and the chemotherapeutic agent is injected with the syringe into the malignant mass through a hole made in the abdominal wall of a patient during laparoscopic surgery; or
(v) a carcinoma or sarcoma of esophagus, stomach, duodenum, small intestine, and the chemotherapeutic agent is injected with the needle into the malignant mass through an enteroscope or via a long syringe through a hole made in the abdominal wall of a patient during laparoscopic surgery or is injected through a hole made in a thoracic wall of a patient during thorascopic surgery;
(vi) a carcinoma or sarcoma of the large intestine and rectum, and the chemotherapeutic agent is injected with the needle into the malignant mass through colonoscopy or is injected using a syringe through a hole made in the abdominal wall of a patient during laparoscopic surgery; or
(vii) a carcinoma or sarcoma of the lung, trachea, nasopharynx or larynx and the chemotherapeutic agent is injected into the malignant mass using the needle of a fiber bronchoscope into the malignant mass; or is injected through a hole made in the thoracic wall of a patient; or
(viii) a carcinoma or sarcoma of the urinary bladder, and the chemotherapeutic agent is injected into the malignant mass with a needle through a cystoscope, or is injected through a hole made in the abdominal wall of a patient during laparoscopic surgery; or
(ix) a carcinoma or sarcoma of uterus, and the injectable formulation of chemotherapeutic agent is injected into the malignant mass with a syringe or a needle of a hysteroscope; or is injected through a hole made in the abdominal wall of a patient during laparoscopic surgery; or
(x) a carcinoma or sarcoma of nasopharynx and larynx, and the chemotherapeutic agent is injected into the malignant mass with a needle through a laryngoscope; or
(xii) a carcinoma of the brain, and the chemotherapeutic agent is injected with a needle of a syringe or a fiberscope into the malignant mass after a hole is drilled in the corresponding bone of a skull with the use of an X-ray, CT scan or MR scan; or
(xii) a malignant lymphoma or lymph node with metastasis, and the chemotherapeutic agent is injected into the malignant mass using a needle through the skin of a patient or is injected through a hole made in the abdominal wall of a patient during laparoscopic surgery or through a hole made in the thoracic wall of a patient during thoracoscopic surgery.

### Claim 11

A stable intratumor injectable formulation of a water insoluble chemotherapeutic agent, consisting of a therapeutically effective amount of a chemotherapeutic agent selected from a taxane, a podophyllotoxin derivative, a camptothecin derivative, and mixtures thereof in a pharmaceutically acceptable biocompatible carrier for injection comprising a medium chain triglyceride or a pharmaceutically acceptable vegetable oil, and an optional solvent which when included consists of a non-aqueous solvent, wherein the injectable formulation is stable and suitable for intratumor administration as a solution and is a colorless and transparent non-aqueous solution that does not include cholesterol, a phospholipid, a protein, or surfactant.

### Claim 12 (depends on 11)

The intratumor injection formulation of claim 11, wherein the taxane is paclitaxel.

### Claim 13 (depends on 11)

The intratumor injection formulation of claim 11, wherein the chemotherapeutic agent is paclitaxel and the pharmaceutically acceptable biocompatible carrier for injection is a medium chain triglyceride is an esterification product of an acid selected from the group consisting of caproic acid, caprylic acid, capric acid, lauric acid, and mixtures thereof, further comprising a hydroalcoholic solvent.

### Claim 14 (depends on 11)

The intratumor injectable formulation of claim 11, wherein the chemotherapeutic agent is hydroxycamptothecin and the pharmaceutically acceptable biocompatible carrier for injection comprises a medium chain triglyceride.

### Claim 15 (depends on 11)

The intratumor injection formulation of claim 11, wherein the taxane is doxetaxel.

### Claim 16 (depends on 11)

The intratumor injectable formulation of claim 11, wherein the podophyllotoxin derivative is selected from the group consisting of etoposide, teniposide, and mixtures thereof.

### Claim 17 (depends on 11)

The intratumor injectable formulation of claim 11, wherein the camptothecin derivative is hydroxycamptothecin.

### Claim 18

An intratumor injectable formulation kit, comprising a first vial containing a powdered water insoluble chemotherapeutic agent selected from a taxane, a podophyllotoxin derivative, a camptothecin derivative, and mixtures thereof, and a second vial containing the pharmaceutically acceptable excipients needed to deliver the chemotherapeutic agent to a tumor, the pharmaceutically acceptable excipients consisting of a pharmaceutically acceptable biocompatible carrier comprising a medium chain triglyceride or a pharmaceutically acceptable vegetable oil, and an optional solvent which when included consists of a non-aqueous solvent, wherein the injectable formulation is suitable for intratumor administration as a solution that is stable, colorless, transparent and non-aqueous and does not include cholesterol, a phospholipid, a protein, or surfactant.

### Claim 19 (depends on 11)

The intratumor injectable formulation of claim 11, which further comprises a buffer to provide a pH from about 3.5 to about 4.5.

### Claim 20 (depends on 19)

The intratumor injectable formulation of claim 19, wherein the buffer comprises citric acid.

### Claim 21 (depends on 11)

The formulation of claim 11, wherein the injectable solution is capable of being passed through a 0.22-micron filter.

### Claim 22 (depends on 19)

The formulation of claim 19, wherein the chemotherapeutic agent is paclitaxel, the pharmaceutically acceptable biocompatible carrier for injection is a medium chain triglyceride, and the solvent is dehydrated ethanol.

### Claim 23 (depends on 18)

The intratumor injectable formulation of claim 18, which further comprises a buffer to provide a pH from about 3.5 to about 4.5.