Detail Description of the Invention

Definitions

A "skin condition" or "skin condition characterized by inflammation" as used herein refers to a skin condition characterized by redness, localized heat, swelling, pain, and itching.

An "extract" as used herein refers to the product, as an essence or concentrate, prepared any suitable method for extraction, including, but not limited to cold or hot aqueous extraction. The extract further may be a solution (aqueous) of essential constituents of a complex material (the Convolvulus soldanella) prepared the extraction method.

"Aqueous" as used herein refers to a solution including water. Examples of aqueous extraction solvents include distilled water, and mixtures of water with ethanol, phenol, and other alcohols.
The term "treatment" refers to inhibiting or arresting the development of a disease or condition in a patient, particularly a human, causing regression of the disease or condition, or relieving the symptoms associated with the disease or condition.

II. Compositions and Methods for Treatment of Skin Conditions

In one aspect, the invention provides simple, inexpensive, and safe methods and compositions for treating patients suffering from a skin condition such as eczema or psoriasis.

A. Compositions
The composition is one that includes an extract of sea bindweed Convolvulus soldanella (also called Calystegia soldanella). As will be illustrated below, this compound has been found to effectively reverse or reduce the symptoms of skin conditions such as eczema and psoriasis.

Sea bindweed is a perennial dicotyledonous vine of the morning-glory family that grows on sandy sea-shores. It has been used as a diuretic, laxative, purgative, and to treat scurvy.

In studies conducted in support of the invention, compositions comprised of sea bindweed extract were prepared and administered to test subjects, as set forth in Examples 1-7. The test composition used in Examples 1-7 was comprised of a 30X extract of Convolvulus soldanella prepared by water extraction of the leaves and stems followed by condensation under low pressure and dehydration to form the powder used. In Example 1, 9 patients suffering from eczema (7 adults and 2 children) and 6 patients suffering from psoriasis was treated with 500 to 2000 mg of the bindweed extract two or three times daily for three months. At the end of the treatment period, all of the eczema patients and five of the psoriasis patients reported an improvement in symptoms. Most of the patients reported an improvement after three days (eczema patients) or one to two weeks (psoriasis) of treatment.

In another study, detailed in Example 2, a patient suffering severe eczema over 70% of the body was treated with 2000 mg of the bindweed extract composition three times daily for a period of 6-7 weeks. After treatment, the patient showed no visual evidence of the eczema.

A patient suffering from eczema, as detailed in Example 3, was treated with 2000 mg the bindweed extract composition twice daily for two months. After treatment, the patient showed almost no visual evidence of the eczema.
As described in Example 4, a patient suffering from eczema with open sores on the scalp was treated with 2000 mg of the bindweed extract composition three times daily. After three weeks of treatment, the patient's sores had healed.

In Example 5, a patient suffering eczema on the face and lower legs was treated with 500 mg of the bindweed extract composition three times daily. The patient's symptoms improved after one week of treatment and after two months of treatment showed no visual sign of the eczema.

As detailed in Example 6, a patient suffering from psoriasis over 70% of the body was treated with 2000 mg of bindweed extract, three times daily. The patient's symptoms were improved after five days of treatment and after three months of treatment showed almost no visual sign of the psoriasis.

A patient suffering from severe psoriasis with 80% skin cover, as detailed in Example 7, was treated with 2000 mg of the bindweed extract three times daily. After three months of treatment, the patient's symptoms were in remission and the patient showed no visual signs of the psoriasis.

B. Eczema

Eczema includes certain kinds of dermatitis that involves an inflammation of the skin. Symptoms include dryness, flakiness, heat, blisters, and itching. In mild forms the skin is dry, hot and itchy, while in more severe forms the skin can become broken, raw and bleeding. Examples of eczema include atopic eczema, allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, varicose eczema, and discoid eczema, which are further described below. The causes of eczema are many and varied, and depend on the particular type of eczema. Causes include heredity, allergens, irritants such as chemicals and detergents, allergens such as nickel, and yeast growths. In later years, varicose eczema may be caused by a blood circulatory problems in the legs. Other factors such as environmental factors and stress may further cause eczema.
Currently, there are a number of ways to manage eczema, including emollients, topical and oral steroids, topical immunomodulators such as tacrolimus and pimecrolimus, UV light, and anti-histamines, creams, ointments, and shower and bath oils for moisturizing the skin, evening primrose oil supplements, phototherapy, immune system suppressants including cyclosporin, and antibiotics for infections resulting from eczema.

The most common types of eczema include:

1. Atopic eczema
Atopic eczema is the most common form of eczema affecting about 10% of infants and about 3% of adults in the United States. One of the most common symptoms of atopic eczema is its itchiness (or pruritis), which can be extremely severe. Other symptoms include overall dryness of the skin, redness and inflammation. Scratching the inflammation can cause the skin to split, leaving it prone to infection. In infected eczema the skin may crack and weep (known as 'wet' eczema). The rash occurs mainly on the face and scalp in infancy and on the on the hands and feet in teens and adults, however, patches can appear anywhere. Although these are the most common sites, any area such as the bends of the elbows, backs of the knees, ankles, wrists, face, neck, and upper chest may also be affected.
Atopic eczema is thought to be a hereditary condition, being genetically linked. People with atopic eczema may further be sensitive to allergens in the environment which are harmless to others. In atopy, there is an excessive reaction by the immune system producing the skin inflammation. Asthma and hayfever may be associated with atopy.

2. Allergic contact dermatitis
Allergic contact dermatitis develops when the body's immune system reacts to a substance in contact with the skin. This allergic reaction often develops over a period of time through repeated contact with the substance. For example, an allergic reaction may occur to nickel, which is often found in earrings, belt buckles and jeans buttons. Reactions can also occur after contact with other substances such as perfumes and rubber.

3. Irritant contact dermatitis
Irritant contact dermatitis is a form of eczema caused by frequent contact with everyday substances, such as detergents and chemicals, which are irritating to the skin. It most commonly occurs on the hands of adults and can be prevented by avoiding the irritants and keeping the skin moisturized.

4. Infant seborrhoeic eczema
Infant seborrhoeic eczema is a common condition affecting infants under one year old, although the exact cause is unknown. Also referred to as cradle cap, it usually starts on the scalp or the nappy area and can quickly spread to other parts of the body. Although this type of eczema looks unpleasant, it does include the symptoms of soreness or itch. This type of eczema normally clears up after a few months without recurrence. The use of moisturizing creams and bath oils has been found to speed the recovery.

5. Adult seborrhoeic eczema
Adult seborrhoeic eczema characteristically affects adults between the ages of 20 and 40. It is usually seen on the scalp as mild dandruff, but can spread to the face, ears and chest. The skin becomes red, inflamed and starts to flake. The condition is believed to be caused by a yeast growth.

6. Varicose eczema
Varicose eczema affects the lower legs of adults in their middle to late years, and is generally caused by poor circulation. Commonly the skin around the ankles is affected, becoming speckled, itchy and inflamed. Untreated skin can break down, resulting in an ulcer.

7. Discoid eczema
Discoid eczema is usually found in adults and appears suddenly as a few coin shaped areas of red skin, normally on the trunk or lower legs. The areas become itchy and can weep fluid.

C. Psoriasis

Psoriasis is a chronic immune-mediated, genetic disease manifesting in the skin and/or the joints affecting more than 4.5 million in the United States. A family association exists in one out of three cases. Psoriasis is a non-contagious and life-long skin disease that has different forms. Symptoms often develops between the ages of 15 and 35, although they can develop at any age. Symptoms include patches of raised red skin covered by a flaky white buildup. In certain kinds of psoriasis, symptoms include a raised, red area (pustular psoriasis) or burned (erythrodermic) appearance. Other symptoms include intense itching and burning. Some people may have a spot or two, while others may have extensive coverage on their body. In general, symptoms are frequently found on the knees, elbows, scalp, hands, feet or lower back. Physically, if less then 2 percent of the body is involved, the case is considered mild. Between 3 and 10 percent is considered moderate, and more than 10 percent is severe.

There are five different types of psoriasis. The most common form of psoriasis (about 80%) is called "plaque psoriasis," which is characterized by well-defined patches of red, raised skin from parakeratosis. Parakeratosis refers to the increased production and movement of skin cells. In normal skin, the outer layer, made up mostly of cells called keratinocytes, is replaced every 27 to 28 days with newly formed keratinocytes. With parakeratosis, this process is sped up to about 3 or 4 days. These cells are moved to the surface faster than they can be incorporated in the skin layer, thus the keratinocytes accumulate and form scaling or lesions. Other symptoms include dilated small blood vessels and inflammatory cells. Plaque psoriasis can appear on any skin surface, although the knees, elbows, scalp, trunk and nails are the most common locations. The other types of psoriasis are guttate, which presents as small, red, individual drops on the skin; inverse smooth, which presents as dry areas of skin, often in folds or creases, that are red and inflamed but do not have scaling; erythrodermic periodic, which presents as widespread, fiery redness of the skin; and pustular, which involves either generalized, widespread areas of reddened skin, or localized areas, particularly the hands and feet (palmo-plantar pustular psoriasis)
Current methods of treatment include moisturizing creams and lotions, synthetic vitamin D, coal tar, anthralin, topical and oral steroids, phototherapy, UV light therapy, retinoids, PUVA (psoralen and UVA light therapy), methotrexate, immunosuppressants such as cyclosporine, and cortisone compounds.

D. Angiogenesis

Angiogenesis refers to the formation and the growth of new blood vessels. This process is an important natural process. Angiogenesis occurs in the healthy body for healing wounds and for restoring blood flow to tissues after injury or insult. The healthy body controls angiogenesis through angiogenesis-stimulating growth factors and angiogenesis inhibitors. Many disease states, such as cancer, diabetic blindness, age-related macular degeneration, rheumatoid arthritis, and psoriasis, are characterized by excessive angiogenesis. In these conditions, new blood vessels feed diseased tissues, destroy normal tissues, and in the case of cancer, the new vessels allow tumor cells to escape into the circulation and lodge in other organs (tumor metastases) (Angiogenesis Foundation www.angio.org).
It has been suggested that the high molecular extracts of Convolvulus arvensis (field bindweed) can be used to inhibit the growth of tumor cells and blood vessels (Meng et al., U.S. Patent No. 6,083,510).
As described in Example 8, a study was conducted in support of using the composition of the invention for inhibiting angiogenesis. In this assay, compositions comprised of sea bindweed extract were compared in a chick chorioallantoic membrane (CAM) assay with C-statin, an extract of Convolvulus arvensis (Meng, et al., 2000). The test composition used in Example 8 was comprised of a 10X extract of Convolvulus soldanella prepared by water extraction of the leaves and stems followed by condensation under low pressure and dehydration to form the sea bindweed extract. Observation of the CAM assay revealed that C-statin inhibited angiogenesis by 20%, while the sea bindweed extract inhibited angiogenesis by 100%.

E. Administration

Symptoms associated with such skin conditions are treated or alleviated by the method described herein.

In accord with the invention, a composition containing sea bindweed extract is formulated into a preparation suitable for administration to a patient suffering from a skin condition such as eczema or psoriasis. The composition can be formulated for any desired mode of administration, discussed in more detail below. Solid, liquid, and semi-solid preparations are contemplated and readily prepared by those of skill in the art. As illustrated by the studies set forth in Examples 1-7, discussed above, the compositions effectively arrest the symptoms associated with skin conditions such as eczema and psoriasis and cause a reduction in these symptoms. Accordingly, the invention contemplates a method of treating skin conditions such as eczema and psoriasis by administering a composition comprising an extract of sea bindweed in an amount effective to arrest the symptoms associated with these skin conditions. The bindweed extract may be administered alone or in combination with conventional therapies.

As illustrated in Example 8, discussed above, the method of the invention is further useful for treating or reducing the symptoms associated with angiogenesis. As described above, the composition for treatment includes an extract from sea bindweed, Convolvulus soldanella. The extract may be prepared from the plant by any known methods. Preferably, 500 to 6000 mg of the extract is administered one to three times daily. In another embodiment, the crude, dried plant may be administered directly.

A preferred method of preparing the extract is aqueous extraction, more preferably water extraction. In one embodiment of this method, an aqueous solvent, preferably distilled water is added to the leaves and/or stems of the Convolvulus soldanella plant. The leaves and stems may be shredded, reduced to fine particles, or homogenized, by known methods like a blender. The leaves and/or stems may be fresh or dried. The plant parts are agitated, pressed, or crushed in the aqueous solution. The plant parts are then filtered from the resulting extract by known means and the supernatant is retained. The extract may also be prepared by a similar process using a heated aqueous solvent. Preferably, a boiling or near-boiling aqueous solution is used. The extract may further be prepared as a decoction by adding the aqueous solvent, adjusting the heat to bring the mixture to a boil or near boil, reduce the heat and simmer for 10-15 min. In another embodiment, the extract is prepared by boiling the plant parts in the aqueous solvent for 10-30 min. In yet another embodiment, the aqueous solvent is added to the plant stems and leaves, the mixture is boiled with stirring and the insoluble matters are removed by filtration or the like to give an extract solution. The extract solution is lyophilized or otherwise concentrated if necessary and spray-dried or freeze-dried in vacuo to give a powder as described in U.S. Patent No. 5,576,241. Alternatively, the extract solution is condensed under low pressure and the solution is dehydrated by any known means, typically freeze drying to prepare a solid. This process may be repeated to prepare a concentrated extract. In yet another embodiment, the fresh juice of the plant is used to prepare the extract. Additionally, the extract may be prepared by any known methods of extraction known in the art, an exemplified by the methods described in Cho et al. Planta Medica, 5:343-345, (1986), incorporated by reference herein.

Routes of delivery include, but are not limited to, various systemic routes, including oral and parenteral routes, e.g., intravenous, subcutaneous, intraperitoneal, and intramuscular, as well as inhalation and transdermal delivery. Administration via these routes is achieved by formulating the compositions into a suitable dosage form. Non-limiting examples include pills, tablets, capsules, suspensions, syrups, buccal/mucosal patches, gels, ointments, suppositories, and the like. Preparation of such dosage forms is routine to those of skill in the art and exemplary references describing preparation of extracts, decoctions, pills, and suspensions are known, such as Chinese Herbal Medicine: Materia Medica; Dan Bensky and Andrew Gamble, ed.; Eastland Press, Seattle, c1986, which is incorporated herein in its entirety. In a preferred embodiment, the composition is administered orally.

Parenteral administration includes injection or gradual infusion over time. The compounds of the invention can be injected intravenously, intraperitoneally, intramuscularly, intratumorally, intranasal or administered transdermally.

The composition may be administered directly to a subject or in a suitable pharmaceutical carrier. In one embodiment, the composition is administered with a physiologically acceptable carrier, excipient, or diluent, where the composition is dissolved or dispersed therein as an active ingredient and formulated according to conventional practice. The carrier may be any of a variety of standard physiologically acceptable carrier employed by those of ordinary skill in the art. It will be understood that the choice of suitable physiologically acceptable carrier will vary dependent upon the chosen mode of administration.

Sustained release compositions are also contemplated within the scope of this application. These may include semipermeable polymeric matrices in the form of shaped articles such as films or microcapsules.

In one embodiment, the composition may be administered at regular intervals, e.g., daily, two times daily or three times daily. In another embodiment, the composition is administered over a period of time, e.g. 6 to 12 months or more. It will be appreciated that administration of the composition may be continued for an indefinite time period. It will be appreciated that dosages of the composition will vary dependent upon the compound used in the composition. Preferred doses for oral administration of the extract is from about 500 mg to 6000 mg on a daily basis.
Dosages will vary in accordance with such factors as the age, health, sex, size and weight of the patient, the route of administration, and the efficacy of the compound with respect to the voltage gated ion-channel. Greater or lesser amounts of the compound may be administered as required.
It will be appreciated that other herbs or ingredients may be administered with the treatment compound.