# US 2014/0193480 A1 · Topical anti-inflammatory compositions and uses thereof

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- Number: US 2014/0193480 A1
- Document ID: US20140193480A1
- Status: Published application
- Kind: A1
- Application number: 14/054,578
- Filed: 2013-10-15
- Published: 2014-07-10
- Earliest claimed: 2011-04-15
- Assignees: Md Matrix Health LLC Dba Md Matrix Health Inc.
- Inventors: Joseph F. McWherter; Uzzi Reiss
- Web page: https://patentgrep.com/patent/US20140193480A1

## CPC

- A61K 31/121: acyclic
- 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 9/0041: {Mammary glands, e.g. breasts, udder; Intramammary administration}
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/09: having two or more such linkages
- A61K 31/12: Ketones
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/26: Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
- A61K 31/353: 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K 31/385: having two or more sulfur atoms in the same ring
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/593: 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
- A61K 36/00: Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines {(antigens from pollen A61K39/36)}
- A61K 36/185: Magnoliopsida (dicotyledons)
- A61K 36/31: Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
- A61K 36/324: Boswellia, e.g. frankincense
- A61K 36/53: Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K 36/61: Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
- A61K 36/752: Citrus, e.g. lime, orange or lemon
- A61K 36/82: Theaceae (Tea family), e.g. camellia
- A61K 36/9066: Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- 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)

## Abstract

Disclosed are pharmaceutical compositions and topical formulations thereof that include multiple, phytochemically-active, nutraceutical compounds, and that possess potent anti-inflammatory and extracellular matrix-stabilizing properties both in vitro and in vivo. Also disclosed are prophylactic and therapeutic methods, as well as dosing regimens and medicaments for use in preventing chronic disease, for treating acute or long-term inflammatory-mediated conditions in affected or at-risk subjects, and for stabilizing one or more components of the mammalian extracellular matrix.

## Claims

### Claim 1

An aqueous composition comprising:
a) one or more catechins, catechin derivatives, or catechin analogs, agonists, or antagonists thereof;
b) one or more curcuminoids, curcuminoid derivatives, or curcuminoid analogs, agonists, or antagonists thereof;
c) one or more isothiocyanates, isothiocyanate derivatives, or isothiocyanate analogs, agonists, or antagonists thereof;
d) one or more stilbenoids, stilbenoid derivatives, or stilbenoid analogs, agonists, or antagonists thereof; and
e) at least one therapeutic essential oil;
wherein each of which present in the composition in an anti-inflammatory-effective amount.

### Claim 2 (depends on 1)

The aqueous composition of claim 1, further comprising one or more cyclodextrins, lipophilic bases, liposomal formulations, polyacrylamide based emulsions, rheology modifiers, transdermal compounding bases or gels, lipoic acid, xanthan gums, cetearyl alcohol, ceteareth-20, isopropyl palmitate, isopropyl myristate, preservatives, or any combination thereof.

### Claim 3 (depends on 1)

The aqueous composition of claim 1, further comprising one or more vitamins, N-methyl-2-pyrrolidone, melatonin, or any combination thereof.

### Claim 4 (depends on 3)

The aqueous composition of claim 3, wherein the one or more vitamins include cholecalciferol, α-tocopherol, β-tocopherol, δ-tocopherol, γ-tocopherol, α-tocotrienol, β-tocotrienol, δ-tocotrienol, γ-tocotrienol, or any combination thereof.

### Claim 5 (depends on 1)

The aqueous composition of claim 1, wherein the one or more catechins include epigallocatechin gallatyl glucoside, or a combination thereof, or wherein the one or more stilbenoids include 3,5,4′-trihydroxy-trans-stilbene, 4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenol, or a combination thereof.

### Claim 6 (depends on 1)

The aqueous composition of claim 1, wherein the one or more curcuminoids include curcumin, tetrahydropiperine, tetrahydrocurcumin, tetrahydrocurcuminoid, tetrahydrodiferuloylmethane, tetrahydro-demethoxydiferuloylmethane, tetrahydrobis-demethoxydiferuloylmethane, or any combination thereof.

### Claim 7 (depends on 1)

The aqueous composition of claim 1, wherein the one or more isothiocyanates include R-sulforaphane, L-sulforaphane, sulforaphene, β-phenylethyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, benzyl isothiocyanate, 6-(methylsulfinyl)hexyl isothiocyanate, tetrahydrodiferuloylmethane, broccoli seed oil, daikon oil, broccoli seed powder, mustard seed oil, or any combination thereof.

### Claim 8 (depends on 1)

The aqueous composition of claim 1, wherein the at least one essential oil includes rosemary essential oil, birch essential oil, balsam fir essential oil, peppermint essential oil, marjoram essential oil, helichrysum essential oil, thyme essential oil, frankincense essential, clove essential oil, turmeric essential oil, orange essential oil, or any combination thereof.

### Claim 9 (depends on 1)

The aqueous composition of claim 1, wherein
a) the one or more catechins is each present in the composition in an amount from about 0.0000001% to about 25%, by weight;
b) the one or more curcuminoids is each present in the composition in an amount from about 0.0000001% to about 25%, by weight;
c) the one or more isothiocyanates is each present in the composition in an amount from about 0.0000001% to about 25%, by weight;
d) the one or more stilbenoids is each present in the composition in an amount from about 0.0000001% to about 25%, by weight; and
e) the at least one essential oil is present in the composition in an amount from 0.0003% to about 50%, by weight.

### Claim 10 (depends on 9)

The aqueous composition of claim 9, wherein
a) the one or more catechins is each present in the composition in an amount from about 0.00001% to about 2.5%, by weight;
b) the one or more curcuminoids is each present in the composition in an amount from about 0.00001% to about 2.5%, by weight;
c) the one or more isothiocyanates is each present in the composition in an amount from about 0.00001% to about 2.5%, by weight;
d) the one or more stilbenoids is each present in the composition in an amount from about 0.00001% to about 2.5%, by weight; and
e) the at least one essential oil is present in the composition in an amount from about 0.003% to about 5%, by weight.

### Claim 11 (depends on 10)

The aqueous composition of claim 10, wherein
a) the one or more catechins is each present in the composition in an amount from about 0.01% to about 0.5%, by weight;
b) the one or more curcuminoids is each present in the composition in an amount from about 0.01% to about 0.5%, by weight;
c) the one or more isothiocyanates is each present in the composition in an amount from about 0.01% to about 0.5%, by weight;
d) the one or more stilbenoids is each present in the composition in an amount from about 0.01% to about 0.5%, by weight; and
e) the at least one essential oil is present in the composition in an amount from about 0.01% to about 0.9%, by weight.

### Claim 12 (depends on 11)

The aqueous composition of claim 11, wherein
a) the one or more catechins is each present in the composition in an amount of about 0.10% to about 0.30% by weight;
b) the one or more curcuminoids is each present in the composition in an amount of about 0.15% to about 0.35%, by weight;
c) the one or more isothiocyanates is each present in the composition in an amount of about 0.3 to about 2%, by weight;
d) the one or more stilbenoids is each present in the composition in an amount of about 0.8% to about 1.2%, by weight; and
e) the at least one essential oil is present in the composition in an amount of about 0.3% to about 0.5%, by weight.

### Claim 13 (depends on 12)

The aqueous composition of claim 12, further comprising one or more of:
f) isopropyl palmitate or isopropyl myristate, in an amount from about 1% to about 10% (by weight);
g) tetrahydropiperine, in an amount from about 0.01% to about 1% (by weight);
h) vitamin D3 or vitamin E, in an amount from about 0.5% to about 2.5% (by weight);
i) 3′3-diindolylmethane, in an amount from about 0.1% to about 1% (by weight); or
j) broccoli seed oil, mustard seed oil, wintercress oil, watercress oil, wintercress seed, watercress seed, or broccoli seed powder, each in an amount from about 0.1% to about 10% (by weight).

### Claim 14 (depends on 1)

The aqueous composition of claim 1, further comprising:
f) isopropyl palmitate and isopropyl myristate, each in an amount from about 1% to about 10%, by weight;
g) tetrahydropiperine, in an amount from about 0.05% to about 1%, by weight;
h) vitamin D3 and vitamin E, each in an amount from about 1.0% to about 2.0%, by weight;
i) 3,3′-diindolylmethane, in an amount from about 0.2% to about 0.75%, by weight; and
j) broccoli seed oil, mustard seed oil, and broccoli seed powder, each in an amount from about 0.2% to about 5%, by weight.

### Claim 15 (depends on 1)

A method for reducing inflammation in a mammalian tissue, or ameliorating at least one symptom in a mammal in need thereof, the method comprising: administering to the mammal, or to a first tissue thereof, an effective amount of the aqueous composition of claim 1, for a time sufficient to reduce inflammation in the mammalian tissue, or to ameliorate the at least one symptom thereof.

### Claim 16 (depends on 15)

The method of claim 15, wherein the at least one symptom thereof includes pain, swelling, redness, edema, aching, tenderness, soreness, or any combination thereof, or wherein the inflammation is caused by, results in, or contributes to, injury, strain, sprain, trauma, soreness, ache, fatigue, cancer, prostatitis, infection, generalized joint pain, temporal mandibular joint pain, arthritis, osteoarthritis, rheumatoid arthritis, or any combination thereof, in an affected mammal.

### Claim 17 (depends on 15)

The method of claim 15, wherein the composition is formulated as an emollient, a cream, an ointment, a lotion, a gel, a salve, a controlled-release matrix, a liposomal or a lipid particle preparation, a microcapsule, or a nanocapsule, a suppository, a transdermal delivery system, or any combination thereof.

### Claim 18 (depends on 15)

The method of claim 15, wherein the mammal exhibits one or more indicia of a disease, a disorder, or a dysfunction that is selected from the group consisting of a pre-menstrual pain, a mammographically-dense breast tissue, a mammary gland inflammation, a fibroid cyst, a lipid cyst, a post-menopausal estrogen insufficiency; a cyclic mastalgia, a benign breast pain, a premenstrual breast pain, a breast tenderness, ache or swelling, a fibrocystic disease or disorder, a mammary nodule or cyst, a fibroadenoma, a mammary carcinoma, a vascular or a neuropathic complication of diabetes, an impairment of fertility, a low production of breast milk, an elevated blood pressure, a restriction of blood flow in the vasculature or microvasculature of an adipose tissue, a menopausal hot flash, a skin or mucous membrane complication of Sjogren's autoimmune syndrome, rosacea, psoriasis, eczema, actinic keratosis, a dermal or peripheral neuropathic complication of shingles, and any combination thereof.

### Claim 19 (depends on 15)

The method of claim 15, wherein the composition is administered to the mammalian tissue in one or more daily doses, each in an amount from about 0.1 cc to about 5 cc, or wherein the composition is administered to the mammalian tissue at least daily for a period of about 14 to about 90 days.

### Claim 20 (depends on 15)

The method of claim 15, wherein the effectiveness of the composition is quantitated, measured, or monitored by thermography, or by comparison of two or more thermographic images of a first tissue of the mammal, at least one of which images is taken pre-treatment, and at least one of which images is obtained either during- or post-treatment.

### Claim 21 (depends on 1)

A method for treating inflammation or ameliorating at least one symptom thereof in a human prostate tissue, a human breast tissue, a human muscle tissue or a human joint, comprising: providing to one or more tissues of a mammal in need thereof, an effective amount of the aqueous composition of claim 1, for a time sufficient to treat the inflammation, or to ameliorate the at least one symptom thereof in the human.

### Claim 22 (depends on 1)

A method for preventing, treating, or ameliorating one or more symptoms of breast microcalcification, ECM damage, trauma, injury, CIS, DCIS, or other neoplastic disorder in a mammal, comprising, providing to the breast tissue of a mammal in need thereof, an effective amount of the aqueous composition of claim 1, for a time sufficient to prevent, treat, or ameliorate the one or more symptoms of the breast microcalcification, ECM damage, trauma, injury, CIS, DCIS, or other neoplastic disorder in the mammal.

### Claim 23 (depends on 1)

A method for promoting or maintaining healthy tissue in a mammal, or for stabilizing the extracellular matrix of a selected tissue in a mammal in need thereof, comprising, providing to the first tissue of the mammal, an amount of the aqueous composition of claim 1, and for a time a) sufficient to promote or maintain healthy tissue in the mammal; or b) effective to stabilize at least one component of a portion of the extracellular matrix of the selected mammalian tissue.