Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 9,10-seco- cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
1999-04-06
2001-07-17
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
9,10-seco- cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
active
06262041
ABSTRACT:
INTRODUCTION
1. Technical Field
This invention relates to the treatment of conditions related to increased oxidative stress and/or antioxidant depletion on epithelial cells by the administration of vitamin D analogs to a human. Thus, a vitamin D analog is used to treat cancer, rosacea and acne and to reduce the rate at which skin ages.
2. Background
The involvement of free radicals and reactive oxygen species in environmental stress conditions such as hyperoxia, hypoxia, reperfusion, heat shock, and metabolism of environmental pollutants and toxic chemicals is well documented. Experimental and clinical evidence also increasingly implicates free radicals in various pathological conditions in skin, such as ionizing irradiation damage, thermal trauma, phototoxic injury, photo allergy, and drug toxicity. This can lead to accelerated aging of the skin, acne, rosacea and/or cancer of the skin. It is known that certain antioxidant defense systems serve to protect skin against free radical-induced damage. It has been noted that individuals with skin types I and II have the yellow-red pigment pheomelanin, which is highly photoreactive and capable of sensitizing free radical production.
Skin antioxidant systems have a finite capacity to reduce oxidative stress or prevent the depletion of natural antioxidants. If oxidative stress persists, the skin's endogenous reserves may be exceeded, and free radical concentrations will increase, leading to cellular damage, such as lipid peroxidation, formation of modified bases in DNA, and DNA strand breaks. Production of hydroxyl- or peroxyl radicals and other activated oxygen species, implicated in the initiation of lipid peroxidation as well as the amount of lipid peroxidation products, such as malondiadlehyde, lipid hydroperoxides, and lipids with conjugated dienes, can be used as markers of cellular damage to indicate the level of damage from oxidative stress.
Increased oxidative stress and antioxidant depletion result in accelerated skin aging which is manifested with skin wrinkling, thickening and sagging, and increased number of senile lentigines (liver spots). Persons with damaged skin and keratinization disorders are at high risk for malignant lesions such as basal and squamous cells carcinoma.
Vitamin D3 is formed in humans by the action of sunlight on skin, and thus its antioxidant action should help protect the cells in which it is formed against the aging and carcinogenic effects of ultraviolet light caused in part by peroxidation of cell membranes.
Vitamin D
3
has the following formula and numbering system:
We have found that the administration of 26,27-hexafluoro-1,25-dihydroxy-vitamin D
3
(also referred to as ST-630) to humans is useful for reducing the rate at which skin ages and for treating acne, rosacea and cancer.
SUMMARY OF THE INVENTION
One aspect of this invention is a pharmaceutical composition for reducing the rate at which skin ages, and for treating acne, rosacea and epithelial cancer, which composition comprises a pharmaceutically-acceptable excipient in combination with ST-630.
Another aspect of this invention is a process for treating acne or rosacea in the skin in a human, which process comprises administering ST-630 to a human in need thereof on a daily basis in an amount sufficient to reduce the severity of the acne or rosacea.
Another aspect of this invention is a process for reducing the rate at which skin of a human ages, which process comprises topically administering ST 630 to the skin of the human on a daily basis in an antioxidative amount for a time sufficient to reduce the rate of skin aging.
Another aspect of this invention is a process for treating epithelial cancer. The process comprises topically administering ST-630 to the epithelial cancer on a daily basis for a time sufficient to alleviate the cancer.
Another aspect of this invention is an article of manufacture that comprises a topical pharmaceutical composition as described in combination with written instructions for performing the process of reducing the rate of skin aging or treating skin cancer, acne or rosacea.
Another aspect is a process for preparing a topically-applied pharmaceutical composition, which process comprises combining ST-630 with a pharmaceutically-acceptable excipient to form a topically-applied composition useful for reducing the rate at which skin ages and for treating acne, rosacea and epithelial cancer.
DESCRIPTION OF SPECIFIC EMBODIMENTS
The compound useful in this invention has the following formula:
The name of the compound is 26,27-hexaflouro-1,25-dihydroxy-vitamin D
3
, also known as ST-630. The compound is described in U.S. Pat. No. 4,358,406 to De Luca et al, which is incorporated herein by reference. The compound may be purchased from Tetrionics, 565 Science Dr., Madison, Wis. 53711. It may also be purchased from Sumitomo Pharmaceuticals Co., 2-3 Doshomachi 2 Chome, Chrio-Ku, Osaka, 541, Japan. The compound will be referred to in this application as ST-630.
A first aspect of this invention is a pharmaceutical composition for administration to a human comprising a combination of a pharmaceutically acceptable excipient and ST-630. The amount of ST-630 present will be determined by the use of the composition. For treating acne in a human, an amount sufficient to decrease the intensity of the condition will be used. For reducing the rate of skin aging, an amount that has an antioxidative effect will be used. For treatment of cancer, an amount having an anticarcinogenic effect is administered. For treating rosacea, an anti-inflammatory amount will be used. Generally, the amount of ST-630 in the composition of this invention will vary from about 0.1 micrograms/gram to about 100 micrograms/gram. The composition may be in a form that is suitable for oral or topical administration, preferably topical. The amount administered over time is discussed hereinafter.
Preferably, the composition is in a form to be administered topically, thus, the composition may be a solution, emulsion (i.e. an ointment, cream or lotion), suspension, gel, or other composition which is applied topically. The pharmaceutical excipients that are useful may be water soluble or water insoluble depending on the desired final product. The dosage form which is prepared in accordance with this invention may be prepared by dissolving the active ingredient in a solvent that is miscible or nonmiscible in water, by suspending the agent in an appropriate medium, or by incorporating the agent into one of the two phases of an oil and water system. In general, it is preferred to prepare a composition which is an emulsion, that is a two-phase system prepared by combining two emulsible liquids, one of which is dispersed uniformly throughout the other. The topically-applied composition is preferably an ointment, i.e., semisolid preparations intended for external application to the skin or mucous membranes.
An ointment encompaases petroleum, i.e., oleaginous bases, emulsion bases—either water-in-oil (W/O) or oil-in-water (O/W)—and the so-called water-soluble bases. Oleaginous bases are described as ointments, but emulsion bases may be termed creams or lotions. The ointment base should be nonirritating, easily removable, nonstaining, stable, non-pH-dependent and compatible with ST-630.
Generally the ointment composition of this invention may be categorized as follows:
Hydrocarbon Bases (Oleaginous)
Example: White Petroleum, White Ointment
1. Emollient
2. Occlusive
3. Nonwater-washable
4. Hydrophobic
5. Greasy
Absorption Bases (Anhydrous)
Examples: Hydrophilic Petrolatum; Anhydrous Lanolin
1. Emollient
2. Occlusive
3. Absorb Water
4. Anyhydrous
5. Greasy
Absorption Bases (W/O [water in oil] Type)
Examples: Lanolin, Cold Cream
1. Emollient
2. Occlusive
3. Contain Water
4. Some absorb additional water
5. Greasy
Water-Removable Bases (O/W Type)
Example: Hydrophilic Ointment
1. Water-washable
2. Nongreasy
3. Can be diluted with water
4. Nonocclusive
Water-Soluble Bases
Example: Polyethylene Glycol Ointment
1. Usually anhydrous
2. Water-soluble and washable
Bertek Pharmaceuticals, Inc.
Cooley & Godward LLP
Goldberg Jerome D.
LandOfFree
Use of vitamin D analogs to treat conditions related to... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of vitamin D analogs to treat conditions related to..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of vitamin D analogs to treat conditions related to... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2513341