# US 11,998,513 B2 · Two-part nitric oxide generating topical compositions

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- Number: US 11,998,513 B2
- Document ID: US11998513B2
- Status: Granted
- Kind: B2
- Application number: 16/976,382
- Filed: 2019-02-28
- Published: 2020-12-31
- Granted: 2024-06-04
- Earliest claimed: 2018-03-01
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Joshua C. Doverspike; James Phan; Jianfeng Wu; Chuanwu Xi; Yu Qin; Mark E. Meyerhoff; Yang Zhou
- Web page: https://patentgrep.com/patent/US11998513B2

## CPC

- A61K 31/04: Nitro compounds
- A61P 17/00: Drugs for dermatological disorders
- A61K 8/23: Sulfur; Selenium; Tellurium; Compounds thereof
- A61K 8/27: Zinc; Compounds thereof
- A61K 8/31: Hydrocarbons
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/30: Zinc; Compounds thereof
- A61K 38/063: {Glutathione}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61Q 19/00: Preparations for care of the skin
- B01J 23/72: Copper
- B01J 31/0272: {containing elements other than those covered by B01J31/0201 - B01J31/0255}
- 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 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 2800/882: Mixing prior to application
- 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
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

A two-part topical composition includes a first composition including a S-nitrosothiol nitric oxide donor and a carrier, and a second composition including zinc oxide. The second composition is to be mixed with the first composition. The zinc oxide reacts with the S-nitrosothiol nitric oxide donor at a temperature ranging from about 20° C. to about 40° C. to enhance a rate of release of nitric oxide from a mixture of the first composition and the second composition.

## Claims

### Claim 1

A two-part topical composition, comprising:
a first composition including a S-nitrosothiol nitric oxide donor and a carrier, wherein the carrier includes petroleum jelly; and
a second composition including zinc oxide, the second composition to be mixed with the first composition at a weight ratio of 50:50 to 80:20;
wherein the zinc oxide is to react with the S-nitrosothiol nitric oxide donor at a temperature ranging from about 20° C. to about 40° C. to enhance a rate of release of nitric oxide from a mixture of the first composition and the second composition.

### Claim 2 (depends on 1)

The two-part topical composition as defined in claim 1 wherein a concentration of the S-nitrosothiol nitric oxide donor in the first composition ranges from about 2.5 wt % to about 40 wt %.

### Claim 3 (depends on 1)

The two-part topical composition as defined in claim 1 wherein a concentration of the zinc oxide in the second composition ranges from about 5 wt% to about 40 wt %.

### Claim 4 (depends on 1)

The two-part topical composition as defined in claim 1 wherein:
the S-nitrosothiol nitric oxide donor is selected from the group consisting of S-nitroso-N-acetyl-penicillamine, S-nitrosoglutathione, and combinations thereof; and
the carrier is the petroleum jelly.

### Claim 5 (depends on 1)

The two-part topical composition as defined in claim 1 wherein the second composition further includes mineral oil, petrolatum, beeswax, dimethicone, sorbitan sesquioleate, microcrystalline wax, PEG-30 dipolyhydroxy stearate, aloe barbadensis leaf extract, glycerin, tropolone, tocopheryl acetate, 1,2-hexanediol, caprylyl glycol, magnesium sulfate, potassium hydroxide, and phenoxyethanol.

### Claim 6 (depends on 1)

The two-part topical composition as defined in claim 1 wherein the second composition further comprises a copper catalyst or an organoselenium catalyst.

### Claim 7

A topical composition kit, comprising:
a first container having therein a first composition including a S-nitrosothiol nitric oxide donor and a carrier, wherein the carrier includes petroleum jelly; and
a second container having therein a second composition including zinc oxide, the second composition to be mixed with the first composition at a weight ratio of 50:50 to 80:20;
wherein the first and second containers respectively deliver effective amounts of the first and second compositions, wherein the zinc oxide reacts with the S-nitrosothiol nitric oxide donor at a temperature ranging from about 20° C. to about 40° C. to enhance a rate of release of nitric oxide from a mixture of the first composition and the second composition.

### Claim 8 (depends on 7)

The topical composition kit as defined in claim 7 wherein the second composition further includes mineral oil, petrolatum, beeswax, dimethicone, sorbitan sesquioleate, microcrystalline wax, PEG-30 dipolyhydroxystearate, aloe barbadensis leaf extract, glycerin, tropolone, tocopheryl acetate, 1,2-hexanediol, caprylyl glycol, magnesium sulfate, potassium hydroxide, and phenoxyethanol.

### Claim 9 (depends on 7)

The topical composition kit as defined in claim 7 wherein the effective amounts of the first composition to the second composition correspond to the weight ratio.

### Claim 10 (depends on 7)

The topical composition kit as defined in claim 7 wherein a concentration of the S-nitrosothiol nitric oxide donor in the first composition ranges from about 2.5 wt % to about 40 wt %.

### Claim 11 (depends on 7)

The topical composition kit as defined in claim 7 wherein a concentration of the zinc oxide in the second composition ranges from about 5 wt % to about 40 wt %.

### Claim 12 (depends on 7)

The topical composition kit as defined in claim 7 wherein:
the S-nitrosothiol nitric oxide donor is selected from the group consisting of S-nitroso-N-acetyl-penicillamine, S-nitrosoglutathione, and combinations thereof; and
the carrier is the petroleum jelly.

### Claim 13

A method for regulating nitric oxide release from a topical composition, the method comprising:
mixing an effective amount of a first composition including a S-nitrosothiol nitric oxide donor and a carrier that includes petroleum jelly with an effective amount of a second composition including zinc oxide to form a mixture, the effective amounts of the first composition to the second composition correspond to a weight ratio ranging from about 50:50 to about 20:80; and
heating the mixture to a temperature ranging from about 20° C. to about 40° C.

### Claim 14 (depends on 13)

The method as defined in claim 13 wherein:
a concentration of the S-nitrosothiol nitric oxide donor in the first composition ranges from about 2.5 wt % to about 40 wt %.

### Claim 15 (depends on 13)

The method as defined in claim 13 wherein:
the S-nitrosothiol nitric oxide donor is selected from the group consisting of S-nitroso-N-acetyl-penicillamine, S-nitrosoglutathione, and combinations thereof; and
the carrier is the petroleum jelly.

### Claim 16

A method for treating a skin ailment, the method comprising:
mixing an effective amount of a first composition including a S-nitrosothiol nitric oxide donor and a carrier that includes petroleum jelly with an effective amount of a second composition including zinc oxide to form a mixture, the effective amounts of the first composition to the second composition correspond to a weight ratio ranging from about 50:50 to about 20:80; and
applying the mixture to skin, whereby the mixture is heated to a temperature ranging from about 20° C. to about 40° C. and the zinc oxide reacts with the S-nitrosothiol nitric oxide donor to enhance a rate of release of nitric oxide.

### Claim 17 (depends on 1)

The two-part topical composition as defined in claim 1 wherein the carrier further includes an ointment containing bacitracin, neomycin, and polymyxin B in a base of cocoa butter, cotton seed oil, sodium pyruvate, tocopheryl acetate, and additional petroleum jelly.

### Claim 18 (depends on 7)

The topical composition kit as defined in claim 7 wherein the carrier further includes an ointment containing bacitracin, neomycin, and polymyxin B in a base of cocoa butter, cotton seed oil, sodium pyruvate, tocopheryl acetate, and additional petroleum jelly.

### Claim 19 (depends on 13)

The method as defined in claim 13 wherein the carrier further includes an ointment containing bacitracin, neomycin, and polymyxin B in a base of cocoa butter, cotton seed oil, sodium pyruvate, tocopheryl acetate, and additional petroleum jelly.