# US 10,500,183 B2 · Acetylcholinesterase inhibitors for treatment of dermatological conditions

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- Number: US 10,500,183 B2
- Document ID: US10500183B2
- Status: Granted
- Kind: B2
- Application number: 15/319,897
- Filed: 2015-06-18
- Published: 2017-05-18
- Granted: 2019-12-10
- Earliest claimed: 2014-06-19
- Assignees: Attillaps Holdings
- Applicants: Attillaps Holdings
- Inventors: Frank Anthony Spallitta
- Web page: https://patentgrep.com/patent/US10500183B2

## CPC

- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61K 9/02: Suppositories; Bougies; Bases therefor; {Ovules}(apparatus for making A61J3/08; devices for introducing into the body A61M31/00)
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 31/683: Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K 36/185: Magnoliopsida (dicotyledons)
- A61K 36/324: Boswellia, e.g. frankincense
- A61P 17/00: Drugs for dermatological disorders
- 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

Embodiments of the invention involve treating skin afflictions by the topical or oral use of acetylcholinesterase inhibitor. By effectively reducing or eliminating the population of Demodex mites in affected skin areas and areas where Demodex mites may exist, this treatment achieves a more complete remission of clinical signs and symptoms of the skin afflictions than any previously described method. Embodiments of the invention are useful for treating skin afflictions including common acne, seborrheic dermatitis, perioral dermatitis, an acneform rash, transient acantholytic dermatosis, acne necrotica milliaris, psoriasis, steroid induced dermatitis, primary irritation dermatitis and rosacea.

## Claims

### Claim 1

A method of treating a skin affliction associated with Demodex brevis and/or Demodex folliculorum mites comprising a step of topically-applying to an individual having the skin affliction an acetylcholinesterase inhibitor selected from the group consisting of physostigmine, demecarium, donepezil, tacrine, echothiophate, diisopropyl fluorophosphate, lactucopicrin, boswellia, celastrus paniculatus, coumarins, galantamine, and huperzine A, or a prodrug or pharmaceutically acceptable salt thereof, in a dosage effective to inactivate Demodex brevis and/or Demodex folliculorum mites in hair follicles and/or skin of the individual, resulting in amelioration or cessation of the manifestations of allergic and/or vasomotor responses to the mites that cause symptoms and signs of the skin affliction in the individual.

### Claim 2 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is efficiently transported into the epidermis or a subdermal region upon contact with said hair follicles and/or skin of the individual.

### Claim 3 (depends on 1)

The method of claim 1, wherein said step of topically-applying said acetylcholinesterase inhibitor kills at least a portion of said demodex brevis and/or demodex folliculorum mites or renders at least a portion of said demodex brevis and/or demodex folliculorum mites unable to reproduce.

### Claim 4 (depends on 1)

The method of claim 1, wherein said step of topically-applying said acetylcholinesterase inhibitor kills and eliminates said demodex brevis and/or demodex folliculorum mites.

### Claim 5 (depends on 1)

The method of claim 1, wherein the skin affliction is one or more of common acne, seborrheic dermatitis, perioral dermatitis, an acneform rash, transient acantholytic dermatosis, acne necrotica milliaris, steroid induced dermatitis, primary irritation dermatitis or rosacea.

### Claim 6 (depends on 1)

The method of claim 1, wherein the skin affliction affects facial skin or eyelids, or both.

### Claim 7 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is a carbamate.

### Claim 8 (depends on 7)

The method of claim 7, wherein said carbamate is a miticide or insecticide.

### Claim 9 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is a naturally occurring compound.

### Claim 10 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is topically applied and the topically-applied acetylcholinesterase inhibitor is formulated in a carrier lotion, cream, soap, wash, shampoo or gel.

### Claim 11 (depends on 10)

The method of claim 10, wherein a concentration of the acetylcholinesterase inhibitor in the topically-applied lotion, cream, soap, wash, shampoo or gel is a lowest concentration effective for killing the demodex mites.

### Claim 12 (depends on 1)

The method of claim 1, wherein the topically-applied acetylcholinesterase inhibitor penetrates an outer layer of the skin of the individual, thereby exposing the demodex brevis and/or demodex folliculorum mites present below the outer layer of the skin to the acetylcholinesterase inhibitor.

### Claim 13 (depends on 12)

The method of claim 12, wherein the topically-applied acetylcholinesterase inhibitor penetrates to a subdermal region of the skin of the individual, thereby exposing the demodex brevis and/or demodex folliculorum mites present in the subdermal region of the skin to the acetylcholinesterase inhibitor.

### Claim 14 (depends on 1)

The method of claim 1, wherein the topically-applied acetylcholinesterase inhibitor is applied to the affected skin areas and/or to non-affected skin areas during a first application period, thereby killing and eliminating adult demodex brevis and/or demodex folliculorum mites from the hair follicles in the skin of the individual, and wherein the topically-applied acetylcholinesterase inhibitor is further applied to the affected skin areas and/or to non-affected skin areas during a second application period, thereby killing and eliminating from the hair follicles and/or skin of the individual demodex brevis and/or demodex folliculorum mites that have matured from a larval form and/or an egg form present on and/or in the skin during the first application period.

### Claim 15 (depends on 1)

The method of claim 1, wherein the acetylcholinesterase inhibitor is topically-applied in a continued intermittent regime sufficient for prophylactic control of demodex mite population in the hair follicles and/or skin of the individual.

### Claim 16 (depends on 1)

The method of claim 1, wherein the inactivation of the demodex brevis and/or demodex folliculorum mites from hair follicles and/or skin of the individual results in a reduction in population of one or more bacteria in the hair follicles and/or skin of the individual.

### Claim 17 (depends on 16)

The method of claim 16, wherein the allergic and/or vasomotor responses to the mites result from a presence of one or more bacteria associated with the mites in the hair follicles and/or skin of the individual.

### Claim 18 (depends on 16)

The method of claim 16, wherein the one or more bacteria comprise one or more bacteria from the genus Staphylococcus or from the genus Bacillus.

### Claim 19 (depends on 16)

The method of claim 16, wherein the one or more bacteria comprise Bacillus oleronius bacteria.

### Claim 20 (depends on 16)

The method of claim 16, wherein the one or more bacteria comprise Staphylococcus epidermidis bacteria.

### Claim 21 (depends on 16)

The method claim 16, wherein the one or more bacteria are present in a digestive system of the demodex brevis and/or demodex folliculorum mites.

### Claim 22

A method of treating a skin affliction associated with Demodex brevis and/or Demodex folliculorum mites comprising a step of topically-applying to an individual having the skin affliction an active ingredient comprising an acetylcholinesterase inhibitor selected from the group consisting of physostigmine, demecarium, donepezil, tacrine, echothiophate, diisopropyl fluorophosphates, lactucopicrin, boswellia, celastrus paniculatus, coumarins, galantamine, and huperzine A, or a prodrug or pharmaceutically acceptable salt thereof, in a dosage sufficient to inactivate Demodex brevis and/or Demodex folliculorum mites in hair follicles and/or skin of the individual, resulting in amelioration or cessation of the manifestations of allergic and/or vasomotor responses to the mites that cause symptoms and signs of the skin affliction in the individual, wherein the topically-applied active ingredient is applied to skin areas affected by the skin affliction and to skin areas not affected by the skin affliction.

### Claim 23 (depends on 22)

The method of claim 22, wherein said active ingredient is a carbamate.

### Claim 24 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is a reversible competitive or noncompetitive inhibitor of acetylcholinesterase.

### Claim 25 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is a quasi-reversible inhibitor of acetylcholinesterase.

### Claim 26 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is Echothiophate, or Diisopropyl fluorophosphate.

### Claim 27 (depends on 1)

The method of claim 1, wherein said acetylcholinesterase inhibitor is selected from the group consisting of: Huperzine A; Galantamine; and Coumarins, or a prodrug or pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

The method of claim 1, wherein the acetylcholinesterase inhibitor has an established safety profile in humans.

### Claim 29 (depends on 22)

The method of claim 22, wherein the acetylcholinesterase inhibitor has an established safety profile in humans.