# US 11,110,064 B2 · Gel formulation for treating diabetic foot ulcer infections

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- Number: US 11,110,064 B2
- Document ID: US11110064B2
- Status: Granted
- Kind: B2
- Application number: 16/221,540
- Filed: 2018-12-16
- Published: 2020-06-18
- Granted: 2021-09-07
- Earliest claimed: 2018-12-16
- Assignees: Srm Institute of Science and Technology
- Applicants: Srm Institute of Science and Technology
- Inventors: Marakanam Srinivasan Uma Shankar
- Web page: https://patentgrep.com/patent/US11110064B2

## CPC

- A61K 9/5078: {with drug-free core}
- 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 9/501: {Inorganic compounds}
- A61K 9/5015: {Organic compounds, e.g. fats, sugars}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5089: {Processes}
- A61K 9/5115: {Inorganic compounds}
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 9/5192: {Processes}
- A61K 31/545: Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-A61K-0953.gif] , e.g. cephalosporins, {cefaclor, or cephalexine}
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to a gel formulation for treating diabetic foot ulcer infections. The gel formulation comprises antibiotic loaded aquasomes, a gelling agent, a preservative, and a fluid medium. The gel formulation of the present disclosure can be used for treating diabetic foot ulcer infections in mammals.

## Claims

### Claim 1

A gel formulation for treating diabetic foot ulcer infections, said formulation comprising:
antibiotic loaded aquasomes having a diameter in the range of 80 nm to 120 nm as measured by a zeta sizer instrument;
a gelling agent;
a preservative; and
a fluid medium,
wherein said antibiotic loaded aquasomes includes antibiotic loaded on a polyhydroxy oligomer coated calcium phosphate,
wherein said polyhydroxy oligomer is selected from the group consisting of lactose, trehalose, and cellobiose,
wherein said antibiotic loaded aquasomes include a calcium phosphate core having a particle diameter in the range of 45 nm to 55 nm as measured by a zeta sizer instrument, coated with polyhydroxy oligomer thereon followed by coating of an antibiotic on said aquasomes,
wherein said aquasomes are in an amount in the range of 15 wt % to 20 wt % of the total weight of said formulation; said gelling agent is in an amount in the range of 70 wt % to 90 wt % of the total weight of said formulation; said preservative is in an amount in the range of 0.05 wt % to 0.25 wt % of the total weight of said formulation; and said fluid medium is in an amount in the range of 1 wt % to 4 wt % of the total weight of said formulation,
wherein the pH of said gel formulation is in the range of 6.0 to 7.0, and
wherein the said the gel formulation is stable over the period of 6 months.

### Claim 2 (depends on 1)

The formulation as claimed in claim 1, wherein said aquasomes are in an amount of 19.4 wt % of the total weight of said formulation; said gelling agent is in an amount of 77.66 wt % of the total weight of said formulation; said preservative is in an amount of 0.2 wt % of the total weight of said formulation; and said fluid medium is in an amount of 2.74 wt % of the total weight of said formulation.

### Claim 3 (depends on 1)

The formulation as claimed in claim 1, wherein said antibiotic is cephalosporin.

### Claim 4 (depends on 1)

The formulation as claimed in claim 1, wherein said antibiotic is selected from cefprozil monohydrate and cefuroxime axetil.

### Claim 5 (depends on 1)

The formulation as claimed in claim 1, wherein said gelling agent is selected from the group consisting of 2-propenoic acid homopolymer, acacia, pectin, methyl cellulose, ethyl cellulose, hydroxyl propyl methyl cellulose, and sodium alginate.

### Claim 6 (depends on 1)

The formulation as claimed in claim 1, wherein said preservative is at least one selected from the group consisting of methyl paraben, propyl paraben, benzoic acid, sodium benzoate, and cholocresol.

### Claim 7 (depends on 1)

The formulation as claimed in claim 1, wherein said fluid medium is selected from the group consisting of water, ethanol, benzene, acetone, and phosphate buffer.

### Claim 8 (depends on 1)

A process for preparing a gel formulation as claimed in claim 1, said process comprising the following steps:
I. preparing antibiotic loaded aquasomes using following steps:
a. reacting disodium hydrogen phosphate solution and calcium chloride solution under continuous stirring to obtain a first mixture comprising precipitated calcium phosphate;
b. separating said precipitated calcium phosphate from said first mixture and washing said precipitated calcium phosphate with water to obtain calcium phosphate;
c. suspending said calcium phosphate in water and filtering to obtain filtered calcium phosphate;
d. lyophilizing said filtered calcium phosphate to obtain a core of calcium phosphate;
e. admixing said core of calcium phosphate and a polyhydroxy oligomer to obtain a second mixture, followed by sonicating said second mixture for a time period in the range of 10 minutes to 20 minutes to obtain a suspension and settling said suspension at a temperature in the range of 2° C. to 8° C. for a time period in the range of 360 minutes to 600 minutes;
f. lyophilizing said settled suspension to obtain a polyhydroxy oligomer coated calcium phosphate;
g. mixing antibiotic and said polyhydroxy oligomer coated calcium phosphate under stirring for a time period in the range of 80 minutes to 100 minutes to obtain a third mixture and settling said third mixture at a temperature in the range of 2° C. to 8° C. for a time period in the range of 360 minutes to 600 minutes; and
h. lyophilizing said settled third mixture to obtain antibiotic loaded aquasomes; and
II. blending said aquasomes of step (I) with a gelling agent, a preservative, and a fluid medium to obtain a gel formulation.

### Claim 9 (depends on 8)

The process as claimed in claim 8, wherein the molar ratio of said disodium hydrogen phosphate solution to said calcium chloride solution is 1:1.

### Claim 10 (depends on 8)

The process as claimed in claim 8, wherein said filtration of step (c) is carried out using 0.22 μm Millipore filter.

### Claim 11 (depends on 8)

The process as claimed in claim 8, wherein particle diameter of said core of calcium phosphate is in the range of 45 nm to 55 nm.

### Claim 12 (depends on 8)

The process as claimed in claim 8, wherein said polyhydroxy oligomer is selected from the group consisting of lactose, trehalose, and cellobiose.

### Claim 13 (depends on 8)

The process as claimed in claim 8, wherein the weight ratio of said polyhydroxy oligomer to said core of calcium phosphate is 1:2.

### Claim 14 (depends on 8)

The process as claimed in claim 8, wherein the weight ratio of said antibiotic to said polyhydroxy oligomer coated calcium phosphate is 1:2.

### Claim 15 (depends on 1)

A method for treatment of diabetic foot ulcer infections in mammals, the method comprising topical application of an effective amount of the gel formulation as claimed in claim 1 to the diabetic foot ulcer.

### Claim 16 (depends on 15)

The method as claimed in claim 15, wherein said effective amount of said gel formulation is in the range of 2 mg to 20 mg.