# US 11,304,959 B2 · Vaginal inserted estradiol pharmaceutical compositions and methods

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- Number: US 11,304,959 B2
- Document ID: US11304959B2
- Status: Granted
- Kind: B2
- Application number: 16/746,434
- Filed: 2020-01-17
- Published: 2020-05-14
- Granted: 2022-04-19
- Earliest claimed: 2012-12-21
- Assignees: TherapeuticsMD, Inc.
- Applicants: TherapeuticsMD, Inc.
- Inventors: Brian A. Bernick; Thorsteinn Thorsteinsson; Peter H. R. Persicaner; Janice Louise Cacace; Frederick D. Sancilio; Neda Irani; Julia Amadio
- Web page: https://patentgrep.com/patent/US11304959B2

## CPC

- A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K 9/0036: {Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- 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

According to various embodiments of this disclosure, pharmaceutical compositions comprising solubilized estradiol are provided. In various embodiments, such compositions are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy.

## Claims

### Claim 1

A vaginal suppository comprising a liquid composition, the liquid composition comprising:
a) about 4 μg of estradiol;
b) about 90 wt % of a mixture of caprylic and capric triglycerides; and
c) about 10 wt % of a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate;
wherein estradiol is the only active hormone in the vaginal suppository.

### Claim 2 (depends on 1)

The vaginal suppository of claim 1, wherein the estradiol is solubilized.

### Claim 3 (depends on 1)

The vaginal suppository of claim 1, wherein the liquid composition has a viscosity between about 50 cps to about 1000 cps at 25° C.

### Claim 4 (depends on 3)

The vaginal suppository of claim 3, wherein the viscosity of the liquid composition is about 90 cps at 25° C.

### Claim 5 (depends on 1)

The vaginal suppository of claim 1 further comprising a gelatin capsule delivery vehicle encapsulating the liquid composition.

### Claim 6

A vaginal suppository comprising a liquid composition, the liquid composition comprising:
a) about 10 μg of estradiol;
b) about 90 wt % caprylic and capric triglycerides; and
c) about 10 wt % of a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate;
wherein estradiol is the only active hormone in the vaginal suppository.

### Claim 7 (depends on 6)

The vaginal suppository of claim 6, wherein the estradiol is solubilized.

### Claim 8 (depends on 6)

The vaginal suppository of claim 6, wherein the liquid composition has a viscosity between about 50 cps to about 1000 cps at 25° C.

### Claim 9 (depends on 6)

The vaginal suppository of claim 6, wherein the viscosity of the liquid composition is about 90 cps at 25° C.

### Claim 10 (depends on 6)

The vaginal suppository of claim 6 further comprising a gelatin capsule delivery vehicle encapsulating the liquid composition.

### Claim 11

A vaginal suppository comprising a liquid composition, the liquid composition comprising:
a) about 4 μg or 10 μg of estradiol or estradiol hemihydrate;
b) about 270 mg of a mixture of caprylic and capric triglycerides; and
c) about 30 mg of a mixture of PEG-6 stearate, ethylene glycol palmitostearate, and PEG-32 stearate;
wherein estradiol is the only active hormone in the vaginal suppository; wherein the mixture of caprylic and capric triglycerides is at an amount of about 90% by weight of the liquid composition and wherein the mixture of PEG-6 stearate, ethylene glycol palmitostearate and PEG-32 stearate is at an amount of about 10% by weight of the liquid composition.

### Claim 12 (depends on 11)

The vaginal suppository of claim 11, wherein the estradiol or estradiol hemihydrate is solubilized.

### Claim 13 (depends on 11)

The vaginal suppository of claim 11, wherein the liquid composition has a viscosity between about 50 cps to about 1000 cps at 25° C.

### Claim 14 (depends on 11)

The vaginal suppository of claim 11, wherein the viscosity of the liquid composition is about 90 cps at 25° C.

### Claim 15 (depends on 11)

The vaginal suppository of claim 11 further comprising a gelatin capsule delivery vehicle encapsulating the liquid composition.