# US 10,441,569 B2 · Self-emulsifying formulations of DIM-related indoles

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- Number: US 10,441,569 B2
- Document ID: US10441569B2
- Status: Granted
- Kind: B2
- Application number: 15/844,365
- Filed: 2017-12-15
- Published: 2018-06-14
- Granted: 2019-10-15
- Earliest claimed: 2015-04-10
- Assignees: BioResponse, L.L.C.
- Applicants: BioResponse, L.L.C.
- Inventors: Michael A. Zeligs; Irwin C. Jacobs
- Web page: https://patentgrep.com/patent/US10441569B2

## CPC

- A61K 31/404: Indoles, e.g. pindolol
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/10: Dispersions; Emulsions
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 31/215: of carboxylic acids
- A61K 31/23: of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K 31/275: Nitriles; Isonitriles
- A61K 31/357: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/59: Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/00: Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- 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 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- 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 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/38: Cellulose; Derivatives thereof
- A61K 47/46: Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed herein are self-emulsifying compositions and formulations of Diindolylmethane (“DIM”) and certain derivatives of DIM, their uses and methods of making. In particular, the disclosed compositions comprise a DIM-related indole as an active agent and a carrier, wherein the carrier comprises a solvent, one or more surfactants with an HLB of greater than 7, and one or more co-surfactants with an HLB equal to or less than 7. In certain aspects of the invention, the compositions disclosed herein show improved bioavailability.

## Claims

### Claim 1

A composition comprising 3,3′-diindolylmethane (“DIM”) as the biologically active agent and a carrier of said active agent, wherein the carrier comprises:
(i) an essential oil, wherein the essential oil is peppermint oil, tea tree oil, wintergreen oil, lemon oil, lime oil, lavender oil, ginger oil, nutmeg oil, fennel oil, eucalyptus oil, rosemary oil, pomegranate seed oil, black cumin oil, clove oil, mustard oil, or cinnamon bark oil,
(ii) a lauroyl polyoxyl-32 glyceride,
(iii) propylene glycol caprylate,
(iv) polysorbate 80 or tocopherol PEG 1000 succinate, and
(v) a lecithin;
wherein the composition, upon dispersion in water or contact with gastrointestinal fluids, emulsifies to form a dispersion of oil-in-water globules.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the essential oil is peppermint oil, lavender oil, ginger oil, nutmeg oil, fennel oil, eucalyptus oil, rosemary oil, black cumin oil, mustard oil, or pomegranate seed oil.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the lecithin is phosphatidyl choline or an excipient enriched in phosphatidyl choline.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the phosphatidyl choline is a phosphatidyl choline preparation from soy or sunflower oil.

### Claim 5 (depends on 1)

The composition of claim 1, which comprises tocopherol PEG 1000 succinate in item (iv), and wherein the essential oil is rosemary oil.

### Claim 6 (depends on 1)

The composition of claim 1, which comprises tocopherol PEG 1000 succinate in item (iv), and wherein the essential oil is peppermint oil.

### Claim 7 (depends on 1)

The composition of claim 1, which comprises polysorbate 80 in item (iv), and wherein the essential oil is rosemary oil, and the lecithin is phosphatidyl choline.

### Claim 8 (depends on 1)

The composition of claim 1, which comprises polysorbate 80 in item (iv), and wherein the essential oil is peppermint oil, and the lecithin is phosphatidyl choline.

### Claim 9 (depends on 1)

The composition of claim 1, which further comprises a retinoid.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the retinoid is retinyl palmitate.

### Claim 11 (depends on 10)

The composition of claim 10, which further comprises Vitamin D.

### Claim 12 (depends on 1)

The composition of claim 1, which further comprises melatonin.

### Claim 13 (depends on 1)

The composition of claim 1, which further comprises Vitamin K2, wherein Vitamin K2 is menaquinone-7.

### Claim 14 (depends on 1)

The composition of claim 1, which further comprises Vitamin D.

### Claim 15 (depends on 1)

The composition of claim 1, which further comprises Vitamin K2 and Vitamin D.

### Claim 16 (depends on 1)

The composition of claim 1, which further comprises ursolic acid, plumbagin or curcumin.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the DIM in the composition is in an amount from 5% to 20% by weight.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the DIM in the composition is in an amount of at least 10% by weight.

### Claim 19 (depends on 1)

The composition of claim 1, wherein at least 50% of the globules are less than 1.5 μm in diameter, or wherein the globules have a mean particle size of less than 1.5 μm in diameter; and wherein the size of the particles is determined by in vitro dispersion testing.

### Claim 20 (depends on 1)

The composition of claim 1, which is formulated for oral administration.

### Claim 21 (depends on 2)

The composition of claim 2, wherein the essential oil is peppermint oil, rosemary oil, ginger oil, or black cumin oil.

### Claim 22 (depends on 20)

The composition of claim 20, which further comprises ethanol.

### Claim 23 (depends on 1)

The composition of claim 1, which further comprises one or more of: ethanol, isopropanol, acetone, ethyl myristate, propylene glycol, diethylene glycol monoethyl ether, and caprylocaproyl polyoxyl-8 glyceride; wherein the composition is formulated for topical administration.

### Claim 24 (depends on 1)

A method for treating acne in a human subject in need thereof comprising administering the composition of claim 1 to the subject.

### Claim 25 (depends on 24)

The method of claim 24 comprising further co-administering retinyl palmitate to the subject.

### Claim 26 (depends on 24)

The method of claim 24, wherein the administering is topical, and wherein the composition is formulated as a wash, a scrub, a shampoo, or a cosmetic or hygiene product for use with water or administration to a wet surface.

### Claim 27 (depends on 1)

A method for treating atopic dermatitis in a mammal in need thereof comprising administering the composition of claim 1 to the subject.

### Claim 28 (depends on 27)

The method of claim 27, wherein the administering is topical, and wherein the composition is formulated as a wash, a scrub, a shampoo, or a cosmetic or hygiene product for use with water or administration to a wet surface.