# US 11,077,061 B2 · Oral rapamycin nanoparticle preparations and use

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- Number: US 11,077,061 B2
- Document ID: US11077061B2
- Status: Granted
- Kind: B2
- Application number: 16/527,398
- Filed: 2019-07-31
- Published: 2019-11-21
- Granted: 2021-08-03
- Earliest claimed: 2013-12-31
- Assignees: Rapamycin Holdings, Inc.
- Applicants: Rapamycin Holdings, Inc.
- Inventors: Dana Vaughn; Neal K. Vail
- Web page: https://patentgrep.com/patent/US11077061B2

## CPC

- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/141: {Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers ((co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50)}
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- 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

Oral preparations of microcapsules and nanoparticles including an inhibitor of the mammalian target of rapamycin. The preparations are intended to assist with the treatment and prevention of cancer, neurocognitive dysfunction, genetically predisposed disorders, and age-related disorders. The embodiments discussed address the present need for alternative preparations or manufacturing processes that ensure efficacy while improving other performance characteristics such as storage stability, biodistribution, dosage cost, etc.

## Claims

### Claim 1

A microparticle pharmaceutical preparation, comprising:
a) an enteric coating comprising a solid excipient matrix, said solid excipient matrix comprising a polymer composition that remains intact when exposed to acidic conditions of the alimentary canal of an animal and that disintegrates in near-neutral to basic conditions of targeted portions of said alimentary canal, said polymer composition comprising a copolymer of methacrylic acid and methyl methacrylate;
b) nanoparticles dispersed within said solid excipient matrix, said nanoparticles comprising:
1) a micelle-inducing compound, said micelle-inducing compound comprising sodium cholate;
2) a pharmaceutically active core comprising rapamycin or an analog of rapamycin;
c) said micelle-inducing compound naturally inducing formation of micelles, said micelles having properties that promote stability of said rapamycin or said analog of rapamycin when said nanoparticles are dispersed within said solid excipient matrix.

### Claim 2 (depends on 1)

The pharmaceutical preparation of claim 1, wherein said nanoparticles are sized in the range between about 1 nanometer to about 1 micron.

### Claim 3 (depends on 1)

The pharmaceutical preparation of claim 1, wherein said copolymer further comprises methacrylic acid and methyl methacrylate at a ratio of 1:2.

### Claim 4 (depends on 1)

The pharmaceutical preparation of claim 1, wherein said copolymer further comprises methacrylic acid and methyl methacrylate at a ratio of 1:1.

### Claim 5 (depends on 1)

The pharmaceutical preparation of claim 1, wherein said polymer composition has a dissolution pH of about 7.

### Claim 6 (depends on 1)

The pharmaceutical preparation of claim 1, wherein said analog of rapamycin is selected from the group consisting of everolimus, temserolimus, tacrolimus, prerapamycin, zotarolimus, ridaforolimus, 7-epi-rapamycin, 7-thiomethyl-rapamycin, 7-epi-trimethoxyphenyl-rapamycin, 7-epi-thiomethyl-rapamycin, 7-demethoxy-rapamycin, 32-demethoxy-rapamycin, 2-desmethyl-rapamycin, and 42-O-(2-hydroxy)ethyl rapamycin, rapamycin oximes, rapamycin aminoesters, rapamycin dialdehydes, rapamycin 29-enols, O-alkylated rapamycin derivatives, water soluble rapamycin esters, alkylated rapamycin derivatives, rapamycin amidino carbamates, biotin esters of rapamycin, carbamates of rapamycin, rapamycin hydroxyesters, rapamycin 42-sulfonates, 42-(N-carbalkoxy)sulfamates, rapamycin oxepane isomers, imidazolidyl rapamycin derivatives, rapamycin alkoxyesters, rapamycin pyrazoles, acyl derivatives of rapamycin, rapamycin amide esters, rapamycin fluorinated esters, rapamycin acetals, oxorapamycins, and rapamycin silyl ethers.