Topical therapeutic compositions containing bromelain

Abstract

Compositions containing bromelain are disclosed for use as topical therapeutic agents to restore healthy skin, and for immediate and extended relief from itching and irritation associated with contact dermatitis, insect bites, idiopathic itch, chronic itch, hives, psoriasis, seborrhea, eczema and cracked fingertips, skin abrasions, cuts and minor burns as well as other indications. The compositions include lotions, creams and ointments.

Claims

1. A topical composition for the relief of itch, inflammation, or irritation, comprising either: (a) between 60 and 300 GDU (gelatin dissolving units) of bromelain per gram; or (b) between 2% and 10% by weight crude bromelain extract; in a dermatologically acceptable ointment, cream or lotion, wherein the composition does not comprise papain.

2. The composition according to claim 1, comprising either: (a) between 100 and 300 GDU of bromelain per gram; or (b) between 3% and 10% by weight crude bromelain extract.

3. The composition according to claim 1, comprising either: (a) between 200 and 300 GDU of bromelain per gram; or (b) between 6% and 10% by weight crude bromelain extract.

4. The composition according to claim 1, comprising either: (a) between 60 and 250 GDU of bromelain per gram; or (b) between 2% and 7.5% by weight crude bromelain extract.

5. The composition according to claim 1, comprising either: (a) between 100 and 250 GDU of bromelain per gram; or (b) between 3% and 7.5% by weight crude bromelain extract.

6. The composition according to claim 5, comprising either: (a) about 180 GDU of bromelain per gram; or (b) about 5% by weight crude bromelain extract.

7. The composition according to claim 1, wherein the dermatologically acceptable carrier is a cream or lotion.

8. The composition according to claim 7, wherein the cream or lotion comprises from 20 to 85 percent water by weight.

9. The composition according to claim 1, further comprising one or more carrier oils selected from the group consisting of grapeseed oil, rice bran oil, sunflower oil, olive oil, soy oil, coconut oil and combinations thereof, in an amount that ranges from 8 to 12 weight percent.

10. The composition according to claim 1, further comprising one or more skin softening agents selected from the group consisting of Shea butter, avocado butter, cocoa butter, illipe butter, mango butter and combinations thereof, in an amount that ranges from 4 to 11 weight percent.

11. The composition according to claim 1, further comprising one or more emulsifiers selected from the group consisting of emulsifying wax NF, glyceryl stearate, cetearyl alcohol, sodium stearoyl lactylate, and combinations thereof, in an amount that ranges from 6 to 8 weight percent.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Before explaining certain embodiments of the invention in detail by way of exemplary tables, experimentation, results, and laboratory procedures, it is to be understood that the invention is not limited in its application to the details of preparation or to the identities and proportions of the components set forth in the following description or illustrated in the examples, tables, experimentation or results. Those of skill in the art will appreciate that the invention is capable of other embodiments, and of being practiced or carried out in various ways. Also, it is to be understood that the phraseology employed herein is for the purpose of description and should not be regarded as limiting.

(2) The present invention is directed to compositions for topical application to the skin and having immediate and long-lasting antipruritic, anti-inflammatory, and skin-restorative properties. The compositions may be in the form of liquids, lotions, creams, ointments or gels. Topical application of the compositions of the invention provide relief of skin irritation, discomfort, itch and other symptoms caused by a variety of conditions, including but not limited to psoriasis, seborrhea, rosacea, eczema, various allergies, dermatitis, winter itch, chronic itch, cracked fingertips, atopic dermatitis (also known as idiopathic itching), insect bites and stings, fire ant bites, and the itch associated with diabetes, as well as itching and irritation associated with burns, wounds and abrasions that are in the process of healing.

(3) Broadly speaking, the compositions of the invention comprise bromelain dispersed or dissolved in a dermatologically acceptable carrier. The compositions of the invention contain between about 60 and 300 GDU (gelatin dissolving units) of bromelain per gram. Thus, by way of example, if the bromelain employed to prepare a composition of the invention contains 1200 GDU bromelain per gram, suitable compositions will contain between 5 and 25 weight percent of this material. Concentrations of bromelain below about 60 GDU per gram have been found to provide unsatisfactory levels of relief, while concentrations in excess of about 300 GDU bromelain per gram, although effective, can be irritating to the skin.

(4) Thus, the compositions of the invention comprise at least about 60 GDU per gram of bromelain in a dermatologically acceptable carrier. The compositions preferably contain at least about 100 GDU bromelain per gram, and more preferably at least about 150 GDU bromelain per gram. Still more preferably, the compositions contain at least about 200 GDU bromelain per gram. In alternative embodiments, the compositions comprise at least about 250 GDU per gram of bromelain.

(5) In order to minimize burning, itching, or irritation due to excessive concentrations of bromelain, the compositions preferably comprise between 60 and 300 GDU of bromelain per gram, and more preferably between 100 and 300 GDU of bromelain per gram. In other embodiments, the compositions may comprise between 200 and 300 GDU of bromelain per gram, between 60 and 250 GDU of bromelain per gram, or between 100 and 250 GDU of bromelain per gram. Particularly preferred compositions comprise about 180 GDU of bromelain per gram.

(6) For convenience, the preparations of the invention may be prepared based upon quantities of crude bromelain extract. When practicing the invention without a measurement of enzyme activity, it will be understood that the quantities set out below are necessarily approximations, and that the activities of the compositions so produced may vary significantly (e.g., by a factor of two) from those prepared on the basis of GDU per gram. With that caveat, the compositions of the invention preferably comprise between 2% and 10% by weight crude bromelain extract, and more preferably between 3% and 10% by weight crude bromelain extract. In other embodiments, the compositions may comprise between 6% and 10% by weight crude bromelain extract, between 2% and 7.5% by weight crude bromelain extract, or between 3% and 7.5% by weight crude bromelain extract. Particularly preferred compositions comprise about 5% by weight crude bromelain extract.

(7) Preferably, the bromelain component of the compositions of the invention is a crude bromelain extract from pineapple fruit, core and/or stem, in which the protein components have not been fractionated or otherwise separated. Examples of crude bromelain extract include, but are not limited to, acetone-, ethanol- and ammonium salt-precipitated powders, filtered and lyophilized plant juices, reverse micellar extracts, and other crude protein isolates prepared by methods known in the art of protein extraction. In these embodiments of the invention, the bromelain compositions contain an array of protease enzymes, as well as natural levels of phosphatase and peroxidase activity, and a complement of protease inhibitors.

(8) The dermatologically acceptable carrier is preferably a cream or lotion. Preferred compositions according to the present invention may comprise an emulsified mixture of water, plant-based fatty acids, triglycerides, emulsifiers, citric acid, potassium sorbate and bromelain.

(9) As used herein, the term “dermatologically acceptable carrier” refers to vehicles, diluents, and carriers known in the art to be suitable for use in dermatological compositions. A dermatologically acceptable carrier can further include adjuvants, additives, and excipients that enhance the carrier's structure and function, including but not limited to buffers, preservatives, gelling agents, rheological modifiers and stabilizers, moisturizers, and humectants. Suitable components are those known in the art to be suitable for use in contact with the skin of humans without undue toxicity, irritation, or allergic response. Suitable materials may be selected from the “Inventory of ingredients employed in cosmetic products,” provided in European Commission Decision 2006/257/EC of Feb. 9, 2006. The dermatologically acceptable carrier may take the physical form of a liquid, lotion, cream, butter, gel or ointment. Water-containing emulsions, in the form of lotions or creams, are preferred carriers, as they permit an effective amount of the composition to be applied to the area of skin in need of treatment, do not rapidly dry out, and maintain contact of the skin with the bromelain for an extended period of time. By moisturizing and softening the stratum corneum, lotions and creams also improve the rate of penetration of bromelain into the epidermis.

(10) Lotion and cream compositions according to the invention contain water, which may be present in amounts ranging from about 20% to about 85% by weight, and an effective amount of an emulsifier, typically from about 2% to about 10% by weight. Preferably, the water is present at 30-75%, and more preferably at 40-60% by weight. The compositions preferably contain a dermatologically acceptable oil, which may be present at between 1% and 20%, preferably between 5% and 15% by weight. Suitable oils are well known in the cosmetic arts, and include but are not limited to grapeseed oil, olive oil, sweet almond oil, avocado oil, sesame oil, canola oil, jojoba oil, and the like, as well as mineral oil and synthetic oils such as dimethicone. The compositions preferably contain a semisolid triglyceride, including but not limited to shea butter, cocoa butter, illipe butter, mango butter, avocado butter or the like, in amounts ranging from about 1% to about 20%, preferably between about 4% and about 15%. A stiffener, such as stearic acid or 12-hydroxystearic acid, may be present, preferably in amounts ranging from 1% to 15%, and preferably between 4% and 10%; the amount may be varied depending on whether a lotion or cream is desired.

(11) Preferably, an emulsifier, such as one or more of emulsifying wax NF, glyceryl stearate, cetearyl alcohol, or sodium stearoyl lactylate, is present in the composition in order to uniformly incorporate water into the ointment. The amount of water may range from about 1% to about 25% by weight, and the emulsion is preferably of the water-in-oil type.

(12) Humectants, including but not limited to glycerin, sugar alcohols, or aloe vera gel, may be present at between 0.5% and 5% by weight. An effective amount, typically 0.4 to 0.8 percent by weight, of one or more preservatives, including but not limited to potassium sorbate, citric acid, propylparaben, methylparaben, diazolidinyl urea, and imidazolidinyl urea, may be present.

(13) Ointment compositions may include any of the oils and triglycerides above, and may further comprise a hydrocarbon base such as hard paraffin, soft paraffin, microcrystalline wax, or ceresin wax. Non-hydrocarbon bases such as wool fat or beeswax may also be employed.

(14) When the composition is a lotion, cream or ointment, it is preferable to prepare a base carrier (the “cosmetically acceptable topical carrier”) and then add the appropriate weight percent of bromelain at a temperature below 25° C. A representative range of formulations of a topical carrier, suitable for use in the present invention, is set out in Table 1:

(15) TABLE-US-00001 TABLE 1 A Cosmetically Acceptable Topical Carrier Ingredient % w/w Shea Butter 4%-11% Grapeseed Oil 8%-12% ECOMulse ™ 6%-8%  Stearic Acid 4%-10% Citric Acid 0.4% Potassium Sorbate 0.4% Distilled water (q.s. to 100%)

EXAMPLES

(16) A cosmetically acceptable topical carrier was prepared by combining distilled water (1575 mL), glycerin (72 g), citric acid (8 g) and potassium sorbate (14 g) in a container and heating this mixture to 70° C. In a separate container, shea butter (45 g), grapeseed oil (240 g), ECOMulse™ (a blend of glyceryl stearate, cetearyl alcohol, and sodium stearoyl lactylate, 174 g) and stearic acid (34 g) were combined and heated to 70° C. The containers were held at 70° C. for 20 minutes. The contents of the two containers were then combined and mixed, and the resulting emulsion was stirred while being allowed to cool to 25° C., resulting in a thick lotion.

(17) The topical carrier thus prepared was combined with a bromelain-maltodextrin powder (381 g) and mixed until homogeneous. The powder used in this example was a product of JRBB Nutrition, distributed by Innate Source Inc., Greeley, Colo., containing 35% bromelain acetone powder by weight (about 333 micrograms of enzyme/g of powder), which assayed at 1200 GDU/g. The resulting composition contained 180 GDU/g bromelain.

(18) Thirty human subjects were recruited, who voluntarily applied the above-described composition to healthy skin and self-reported on the results obtained. After four weeks of three-times-daily application, 100% of subjects reported no redness, itching, burning, or dryness.

(19) Thirty-five human subjects having a variety of skin diseases or syndromes were then recruited, to voluntarily apply the composition to affected skin and self-report on the results obtained. Subjects applied the composition as needed to obtain satisfactory relief; the frequency of application ranged from once daily to four times daily. Subjects reported on any relief obtained, any side effects, and how well the composition performed relative to topical agents previously tried. The results are presented in Table 2:

(20) TABLE-US-00002 TABLE 2 Results of Treatment Frequency Time to Area(s) of Relief relief Days Side Relative Condition Treated Application Obtained (Min) used Effects Other Products Performance Allergy Legs, Arms, When Yes 2 300 None Udder Cream ™, Significantly Chest, Needed Workman's Hands ™, Better Other Aloe, Corticone Cream When Yes 7 120 None Needed Back, Neck When Yes 1 180 None Sarna ™ Somewhat Needed Better Legs, Arms, When Yes 3 400 None Calamine Lotion, Significantly Neck, Back Needed Hydrocorticone Anti- Better Itch Legs, Arms, When Yes 15 450 None Dermalogica Barrier Somewhat Neck, Back, Needed Repair ™ Better Chest Burns Arms When Yes 2 300 None Udder Cream ™, Significantly Needed Workman's Hands ™, Better Aloe, Corticone Cream Legs, Arms, When Yes 3 400 None Calamine Lotion, Significantly Neck, Back Needed Hydrocorticone Anti- Better Itch Legs, Arms, When Yes 15 450 None Benadryl ™ Somewhat Neck, Back, Needed Better Chest Legs, Arms, When Yes 1 210 None Cortaid ™, Aloe Gel, Significantly Chest Needed Benadryl ™ Cream Better Contact Hands 1× Daily Yes 5 20 None Benadryl ™ Significantly Dermatitis Better Legs, Arms, When Yes 20 450 None Cortisone Significantly Neck, Back, Needed Better Chest Legs, Arms, When Yes 1 450 None Cortisone, Significantly Back, Chest Needed Benadryl ™ Better Legs, Arms When Yes 3 300 None Cortisone, Significantly Needed Benadryl ™ Better Legs, Arms, When Yes 15 400 None Cortisone Significantly Neck Needed Better Cracked Hands 2× Daily Yes 400 None None Finger Tips Hands 4× Daily Yes 28 None None Hands 3× Daily Yes 7 120 None Diabetic Itch Legs, Arms, 2× Daily Yes 1 300 None Lac-Hydrin ™ Somewhat Chest Better Eczema Back 1× Daily Yes 1 200 None None Legs, Arms, When Yes 20 450 None Cortisone Significantly Neck, Back, Needed Better Chest Legs, Arms, 2× Daily Yes 1 210 None Cortaid ™, Aloe Gel, Significantly Chest Benadryl ™ Cream Better Back 1× Daily Yes 1 330 None CVS Anti-Itch Lotion, Somewhat Benadryl ™ Better 2× Daily Yes NA Intermit- None tent Arms, Legs, 1× Daily Yes 4 180 None Vaseline Total Significantly Other Moisture ™, Better Lubriderm ™ Feet and 1× Daily Yes 1 10 None Sarna ™ Significantly Ankles Better Back 1× Daily Yes 1 200 None None Idiopathic Back 1× Daily Yes 1 330 None CVS Anti-Itch Lotion, Somewhat Itch Benadryl ™ Better Arms, Legs When Yes 2 300 None Benadryl ™ Significantly Needed Better Legs, Arms, 2× Daily Yes 15 450 None Dermalogica Barrier Somewhat Neck, Back, Repair ™ Better Chest Legs, Arms When Yes 60 320 None BioFreez ™ Significantly Needed Better Legs, Arms 2× Daily Yes 5 150 None Cortisone Significantly Better Legs, Arms, When Yes 3 400 None Calamine Lotion, Significantly Neck, Back Needed Hydrocorticone Anti- Better Itch Legs, Arms, 1× Daily Yes 1 450 None Cortisone, Significantly Back, Chest Benadryl ™ Better Back 1× Daily Yes 5 400 None Sarna ™ anti-itch Significantly lotion, Aveeno ™, Better Eucerin Intensive Repair ™ Legs, Back 1× Daily Yes 1 100 None Itch of a Stomach 1× Daily Yes 1 40 None None healing Incision Insect Bites Legs, Arms When Yes 5 60 None Cortisone, Aloe Significantly Needed Better Legs, Arms, When Yes 1 210 None Cortaid ™, Aloe Gel, Significantly Chest Needed Benadryl ™ Cream Better Arms, Legs, When Yes 4 180 None Vaseline Total Significantly Other Needed Moisture ™, Better Lubriderm ™ Legs, Arms, When Yes 20 450 None Cortisone Significantly Neck, Back, Needed Better Chest Back When Yes 1 Intermit- None Needed tent Legs, Arms When Yes 60 320 None BioFreez ™ Significantly Needed Better Legs, Arms, When Yes 1 450 None Cortisone, Significantly Back, Chest Needed Benadryl ™ Better Legs, Arms When Yes 3 300 None Cortisone, Significantly Needed Benadryl ™ Better Arms, Legs When Yes 2 300 None Benadryl ™ Significantly Needed Better Back, Neck When Yes 1 180 None Sarna ™ Somewhat Needed Better Legs, Arms, When Yes 3 400 None Calamine Lotion, Significantly Neck, Back Needed Hydrocorticone Anti- Better Itch Legs, Arms, When Yes 2 300 None Udder Cream ™, Significantly Chest, Needed Workman's Hands ™, Better Other Aloe, Corticone Cream Legs, Arms, When Yes 15 400 None Cortisone Significantly Neck Needed Better Legs, Arms, When Yes 1 330 None CVS Anti-Itch Lotion, Somewhat Back, Needed Benadryl ™ Better Forehead Legs When Yes 1 Intermit-  None Needed tent Legs, Arms, When Yes 15 450 None Benadryl ™ Somewhat Neck, Back, Needed Better Chest Jellyfish Arms, Legs When Yes 2 300 None Benadryl ™ Significantly Sting Needed Better Joint Pain Legs, Arms 2× Daily No N/A 400 None None Psoriasis When Yes 7 120 None Needed Arms, Legs, 1× Daily Yes 4 180 None Vaseline Total Significantly Other Moisture ™, Better Lubriderm ™ Arms, Legs 1× Daily Yes 1 20 None Cortisone Same Legs, Arms, When Yes 20 450 None Cortisone Significantly Neck, Back, Needed Better Chest Rash Legs, Arms, When Yes 2 300 None Udder Cream ™, Significantly Chest, Needed Workman's Hands ™, Better Other Aloe, Corticone Cream Legs, Arms, When Yes 15 450 None Dermalogica Barrier Somewhat Neck, Back, Needed Repair ™ Better Chest Legs, Arms, When Yes 3 400 None Calamine Lotion, Significantly Neck, Back Needed Hydrocorticone Anti- Better Itch Legs, Arms, When Yes 15 400 None Cortisone Significantly Neck Needed Better Legs, Arms, When Yes 20 450 None Cortisone Significantly Neck, Back, Needed Better Chest Legs, Arms, When Yes 1 210 None Cortaid ™, Aloe Gel, Significantly Chest Needed Benadryl ™ Cream Better Legs, Arms, When Yes 1 450 None Cortisone, Significantly Back, Chest Needed Benadryl ™ Better Legs, Arms When Yes 3 300 None Cortisone, Significantly Needed Benadryl ™ Better Rosacea Face 2× Daily Yes NA 450 None Metronidazole and Significantly Tetracycline Better Face 2× Daily Yes NA 90 None Face 2× Daily Yes NA Intermit- None tent Face 2× Daily Yes NA 90 None Shingles Legs 3× Daily Yes Intermit- None tent Sun Burn Arms, Legs, When Yes 2 Intermit- None Benadryl ™ Significantly Face, Back Needed tent Better Arms, Legs, When Yes 2 Intermit- None Benadryl ™ Significantly Face, Back Needed tent Better

(21) In view of the results obtained, the invention provides a method of relieving itch, inflammation, irritation, and dryness-associated fissures (cracking) of the skin, comprising the topical administration of an effective amount of a bromelain-containing composition of the invention. Several of the experimental subjects also reported a general improvement in the health, color, texture, and cosmetic appearance of their skin, which was significant enough to be commented upon by third parties. The invention more particularly provides a method relieving the symptoms of allergy, burns, contact dermatitis, eczema, cracked fingertips, idiopathic itch, diabetic itch, itch associated with wound healing, insect bites, jellyfish stings, psoriasis, rash, rosacea, shingles, or sunburn, which comprises the topical administration of an effective amount of a bromelain-containing composition of the invention. An effective amount is an amount sufficient to coat the affected area of the skin with a layer of the composition, and will ordinarily be between 0.05 and 1.0 grams per square inch of skin.

(22) Bromelain works by an unknown mechanism to reduce the redness and itching associated with skin irritation caused by a variety of sources. The utility of the invention is not limited to the treatment of insect bites and stings, but appears to include a broad class of itch-associated conditions. The compositions of the invention are expected to be effective for treating psoriasis, rosacea, skin allergies, winter itch, chronic itch, cracked fingertips, eczema (atopic and allergic dermatitis), and other forms of chronic or idiopathic itching, and the itch associated with diabetes and wound healing. Without wishing to be bound by theory, the inventor suggests that bromelain may selectively and rapidly cleave endogenous pro-inflammatory peptides that are over-expressed as a part of the inflammatory response to irritants, and in conditions such as dermatitis, rosacea and psoriasis, and that this, in turn, reduces the erythema, swelling and itching that are associated with these conditions.

(23) The benefits of formulating the active ingredient into a lotion, cream, or ointment are a substantially improved method of application, the ability to keep the active ingredient at the site of injury and the replenishment of natural moisture to the skin, thereby accelerating healing. In preferred embodiments, the use of a limited number of non-allergenic ingredients in a cosmetically acceptable topical carrier decreases the chance of an allergic reaction to the lotion.

(24) The foregoing detailed description has been directed to a particular embodiment of the invention, for the purposes of illustration and explanation. It will be apparent to those skilled in the art that there are obvious modifications and changes in the compositions and processes set forth, the practice of which will not depart from the scope of the appended claims or the spirit of the invention.