AU2002212606A1 - Method for the treatment of inflammation - Google Patents
Method for the treatment of inflammationInfo
- Publication number
- AU2002212606A1 AU2002212606A1 AU2002212606A AU1260602A AU2002212606A1 AU 2002212606 A1 AU2002212606 A1 AU 2002212606A1 AU 2002212606 A AU2002212606 A AU 2002212606A AU 1260602 A AU1260602 A AU 1260602A AU 2002212606 A1 AU2002212606 A1 AU 2002212606A1
- Authority
- AU
- Australia
- Prior art keywords
- dimethicone
- composition
- inflammation
- rpm
- minutes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/695—Silicon compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Description
METHOD FOR THE TREATMENT OF INFLAMMATION
FIELD OF THE INVENTION
The present invention relates to the fields of immunology and pharmacology and more particularly relates to a method for the treatment of inflammation.
BACKGROUND OF THE -INVENTION
Inflammation is a local response to cellular injury that initiates the elimination of noxious agents and damaged tissue. Inflammation is a complex process of physiological and immunological events characterized by capillary dilation, leukocyte infiltration, redness, heat, pain and swelling. Polymorphonuclear neutrophils (hereinafter, "PMNs") and eosinophils are among the list of important mediators of inflammation and release growth factors, cytokines, prostaglandins, leukotrienes and proteases that exacerbate tissue damage. PMN-derived serine proteases such as elastase and cathepsin G are known pathogenic factors in inflammatory and degenerative diseases that include abnormal tissue catabolism.
Although the inflammatory response can be regulated by anti-inflammatory agents such as corticocosteroids, immunosuppressants, non steroidal anti-inflammatory drugs (NSAID), COX-2 inhibitors and protease inhibitors, many of these agents have significant side effects. Corticosteroids may induce Cushingoid features, skin thinning, increased susceptibility to infection and suppression of the hypothalamic-pituitary- adrenal axis. Immunosuppressants may induce hypertension and nephrotoxicity.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 is a bar graph of optical density versus dimethicone concentration showing the inhibitory effect of dimethicone on porcine elastase activity.
Figure 2 A is a bar graph showing the effect of 0, 5.00% and 2.50% dimethicone on PMN phagocytosis in blood samples taken from eight human volunteers. Figure 2B is a bar graph showing the effect of various concentrations of dimethicone on macrophage phagocytosis in blood samples taken from five human volunteers.
Figure 3 is a graph showing the effect of various concentrations of dimethicone on PHA-stimulated PBML proliferation.
Figure 4 is a bar graph of the increase of ear thickness following topical application of hydrocortisone (HC) or various concentrations of dimethicone (DM) showing the effect of hydrocortisone or dimethicone on a delayed-type hypersensitivity reaction in sensitized mice after challenge. The hypersensitivity reaction was an oxazolone- induced hypersensitivity reaction in oxazolone-sensitized mice. Treatment consisted of topical application of the drag twice daily for four days. Figure 5 is a bar graph of the increase of ear thickness following topical application of hydrocortisone (HC) or various concentrations of dimethicone (DM) showing the effect of hydrocortisone or dimethicone on a delayed-type hypersensitivity reaction in sensitized mice after a second challenge. The hypersensitivity reaction was an oxazolone-induced hypersensitivity reaction in oxazolone-sensitized mice. Treatment consisted of topical application of the drug once daily for four days.
Figure 6 is a bar graph of the increase of ear thickness following topical application of hydrocortisone (HC) or various concentrations of dimethicone (DM) showing the effect of hydrocortisone or dimethicone on a delayed-type hypersensitivity reaction in sensitized
mice after a third challenge. The hypersensitivity reaction was an oxazolone-induced hypersensitivity reaction in oxazolone-sensitized mice. Treatment consisted of topical application of the drug once daily for four days. Figure 7 is a graph of body weight of mice during topical application of hydrocortisone (HC) or various concentrations of dimethicone (DM) to oxazolone-sensitized mice after one, two or three challenges with oxazolone and 24, 48 and 72 hours after each challenge.
DETAILED DESCRIPTION OF THE INVENTION
A method for treating an inflammation of skin or a mucous membrane of a mammal, including a human, is provided. In accordance with the method, a composition containing dimethicone and a pharmaceutically acceptable carrier is applied to the skin or mucous membrane in an amount effective to treat inflammation of the skin or mucous membrane. Treatment is useful for reducing, eliminating or preventing inflammation.
As used herein, the word "dimethicone" refers to a silicone oil having a mixture of fully-methylated linear siloxane polymers end- blocked with trimethylsilyloxy units, its analogs, salts, complexes and derivatives and simethicone (a mixture of dimethicone and silicone dioxide).
As used herein the term "dimethicone composition" refers to a composition containg dimethicone and one or more pharmaceutically acceptable carriers.
As used herein, the term "pharmaceutically acceptable" refers to a substance that does not interfere with the physiological effects of dimethicone and that is not toxic to mammals, including humans.
As used herein, the term "inflammation" refers to an inflammatory condition of the skin or of a mucous membrane.
As used herein, the phrases "effective amount" and
"effective to treat" refer to the amount of a dimethicone composition that provides either subjective relief in the symptoms of inflammation as determined by the recipient or objective improvement in the symptoms of inflammation as determined by one skilled in the art.
Dimethicone has been used as an anti-flatulent (U.S. Patent Nos. 5,248,505 and 5,908,636 and PCT Application No. WO9703650A1); as a lubricant (U.S. Patent Nos. 5,922,351, 5,980,944, 5,229,137; European Patent Application Nos. EP571217B1 and EP14253B1; Japanese Patent Application Nos. JP3203048A and JP45230329A; and PCT Application No. WO9610409A3); in hair products (U.S. Patent Nos. 5,658,558, 5,437,809, 5,989,532 and 5,658,558; and Japanese Patent Application No. JP1305019A); and, in cosmetic products (U.S. Patent Nos. 6,007,799, 5,882,666 and 5,208,013; and Japanese Patent Application No. JP1287008A; Disaprio et al. Int. J. Cosemt. Sci. 10:75, 1989). However, until the unexpected discovery described herein, the effectiveness of dimethicone in the treatment of an inflammation of the skin or mucous membranes was not known.
Inflammations suitable for treatment using the method describe herein include, but are not limited to, inflammation of the epidermis, dermis, eye, nasopharynx, gastrointestinal tract and urogenital tract. Such inflammations include, but are not limited to, acne; eczema; gingivitis; psoriasis; pruritus; decubitus ulcer; dermatitis such as allergic dermatitis, contact dermatitis, seborrheac dermatitis and mummular dermatitis; actinic keratosis; actinic lentigos; ichthyoses; ichtyposiformis; Darier maladay; palmoplantary keratodermies; leucoplasies; leucoplasiformis; lichen; blisters; collagen maladies; ultraviolet light damage; rosacea; melasma; comedons; polymorphs; conglobata; infection; sinusitis; dyshidrosis tonsillitis; buccal ulceration; gastrointestinal diseases such as gastric ulceration and inflammatory bowel disease such as colitis, ulcerative colitis, Crohn's disease, enteritis, and haemorrhoids; urogenital
diseases; and, fungal, yeast, bacterial and viral dermatides. Application of the dimethicone composition also is effective in treating wounds, particularly wounds to the skin. Suitable wounds to be treated with the method described herein include, but not limited to, burns, bruises, scrapes, cuts and lacerations.
Most preferably for treatment of the skin, the dimethicone composition is administered topically. Alternatively, depending of course on the mucous membrane to be treated, the dimethicone composition is administered intranasally, intravaginally, intrarectally, or intraoccularly. Topical application includes transdermal or percutaneous delivery such as by application of a percutaneous occlusive patch.
The dimethicone composition to be administered in accordance with the method is formulated using dimethicone and one or more pharmaceutically acceptable carriers by methods known to those skilled in the art, such as, for example, DER-MATOLOGICAL FORMULATIONS: PERCUTANEOUS ABSORPTION, Barry (ed.), Marcel Dekker Inc., 1983 and REMINGTON'S PHARMACEUTICAL SCIENCES). The composition may be in the form of, but is not limited to, a liquid, oil, emulsion, lotion, gel, cream, paste, ointment, foam, powder, aerosol, inhalant, patch or suppositories. The carrier may also be a diluent.
Pharmaceutically acceptable carriers for use in the present invention are known to those skilled in the art. Exemplary carriers can be found in scientific texts such as MERCK INDEX, Merck & Co., Rahway, NJ; and REMINGTON'S PHARMACEUTICAL SCIENCES. Suitable carriers include, but are not limited to, dermophilics; emollients, bactericides, water; saline; and, buffers. Other pharmaceutically acceptable carriers include, but are not limited to, anti-oxidents; coloring agents; dying agents; perfumes; preservatives; tensioactive agents; emulsifying agents such as magnesium aluminum silicate, polyoxyethylene lauryl ether, polyoxyethylene monostearate, polyoxyethylene sorbitan monolaurate, sorbitan monopalmitate, propylene glycol monostearate, sodium borate plus fatty
acid, sodium lauryl sulfate, triethanolamine plus fatty acid, isopropyl myristate and waxes; preservatives such as cresol, propylparaben, methylparaben or sorbic acid; and, stabilizing or thickening agents such as carbomer, cetyl alcohol, glyceryl monostearate, methylcellulose, spermaceti and stearyl alcohol.
Moreover, depending on the proposed use, the dimethicone composition may be administered in conjunction with other active agents including, but not limited to, cicatrizers, local anesthetics, keratolytics, antibiotics, anti-inflammatories, caprylic acid triglyceride, protease inhibitors, antifungals, antiseptics, chemotherapeutics, cytotoxics, nucleosides, immunosuppressors, anti-cancer agents, anti-infectious agents and antihistamines. Preferred anti-inflammatories include nonsteroidal anti-inflammatories, the protein alpha- 1-antitrypsin and hyaluronic acid or analogues thereof. The active agents may be administered before, after, or simultaneously with the dimethicone in separate pharmaceutical formulations or combined in a dimethicone composition formulation and may be additive to or synergistic with dimethicone.
The dimethicone composition is formulated to deliver dimethicone directly onto the inflamed skin or mucous membrane. The dosage of dimethicone used depends on many factors lαiown to those skilled in the art including, but not limited to, the inflammation being treated; the severity of the inflammation; the composition being used; the age, weight and clinical condition of the recipient; and, the experience and judgment of the individual administering the dimethicone. Typically, a single dosage contains from about 0.001 to 40% dimethicone, more preferably from about 0.01 to 25% dimethicone and most preferably from about 0.1 to 15% dimethicone. The amount of dimethicone composition administered is preferably from about 0.01 to 100 ml, more preferably from about 0.05 to 7.5 ml and most preferably from about 0.1 to 5.0 ml. The dimethicone composition may be conveniently presented in a unit dosage form prepared by conventional pharmaceutical
techniques. A dosage of dimethicone can be administered one time or several times to the same recipient. The dosage amount and the dosage schedule can be determined readily by those skilled in the art. Preferred dosage formulations are those containing a dose, sub-dose or fraction thereof of including, but not limited to, the formulations described herein. Further, it should be understood that in addition to the ingredients particularly mentioned herein, the present method can include other agents conventional in the art having regard to the type of formulation being used. The carrier may also include a delayed release material, such as glyceryl monostearate or glyceryl disterearate alone or in combination with a wax. The composition may additionally contain conventional agents such as preservatives (including antioxidizing agents such as tocopherol), thickening agents, wetting and dispersing agents, buffers, humectants, such as lactic acid and glycolic acid copolymers, emulsifying agents, fillers, emollients and surface active agents (such as sorbitane fatty acid esters).
A preferred dimethicone composition is formulated by combining by weight 1 to 50% of a triacylglycerol, wherein the acyl portions are identical or different and represent a caprylyl radical or a capryl radical, 0.8 to 40% of solubilized lanolin alcohol, 1 to 50% of squalene and 0.001 to 25% of dimethicone.
A second preferred dimethicone composition is formulated by combining by weight 1 to 16% of a triacylglycerol, wherein the acyl portions are identical or different and represent a caprylyl radical or a capryl radical, 0.8 to 12.8% of lanolin alcohol solubilized in mineral oil (80% by weight of lanolin in 20% by weight of mineral oil), 1.0 to 16% of squalene, 0.01 to 25% of dimethicone and a buffer.
The following examples will serve to further illustrate the present invention without, at the same time, however, constituting any limitation thereof.
EXAMPLE 1 PREPARATION OF DIMETHICONE OIL
An oil composition containing dimethicone was prepared as follows using the recipe set forth in Table 1.
Table 1 Dimethicone Composition Ingredients
INGREDIENTS % WEIGHT
Dimethicone 10.0 Heavy mineral oil (Ramol 350) 79.4
Isopropyl myristate (emulsifying agent) 10.0
Lanolin alcohol (Amerchol L-101) 0.5
Sorbic acid 0.1
Total 100.0 Isopropyl myristate (INOLEX CHEMICAL CO) was heated to 54 to 60° C in a stainless steel container. Sorbic acid (PENTA MANUFACTURING
COMPANY) was added and mixed until completely dissolved. AMERCHOL L-
101 (CHARLES TENNANT COMPANY CANADA LTD) was added with mixing, the temperature adjusted to 50-55° C, and mixing continued until the preparation was uniform. Dimethicone (SILICONE SF 96-350, GENERAL
ELECTRIC COMPANY) and heavy mineral oil (CANADA COLORS AND
CHEMICALS) were added with mixing and mixing continued for at least 15 minutes or until the preparation was uniform in appearance. The dimethicone composition was transferred to a sterile, screw-cap bottle and stored at room temperature until use.
EXAMPLE 2 PREPARATION OF DIMETHICONE CREAM
A cream composition containing dimethicone was prepared as follows using the recipe set forth in Table 2.
Table 2 Dimethicone Composition Ingredients
INGREDIENTS % WEIGHT
Dimethicone 5.00
Glycerin 8.00
Citric acid anhydrous 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L-101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin B 1 0.50
Purified water 71.29
Total 100.00 Oil phase (phase A):
Atmul 84 (VAN WATERS & ROGERS), Amerchol L-101, cholesterol (CRODA CANADA LTD, Canada), Emulgade 1000 (HENKEL), Eumulgin Bl (HENKEL), dimethicone (Silicone SF 96-350, GENERAL ELECTRIC COMPANY, Canada) were mixed at 72 to 78° C in a heated kettle. Aqueous phase (phase B):
Purified water and glycerin (CANADA COLORS AND CHEMICALS) were added into a reactor, mixed at 25 RPM, and heated. Citric acid (DEBRO, Canada) and edetate disodium (VAN WATER & ROGERS) were added, the temperature brought to 72 to 78° C and the ingredients mixed until uniform. Phase A, at 72 to 78° C, was added to phase B, at 72 to 78° C, homogenized at 1000 RPM for 5 to 10 minutes with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 minutes. The mixture was then cooled to 39 to 41° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35°C, with mixing at 20 RPM for 20 to 30 minutes. The mixture was then cooled to 24 to 28° C, with mixing at 20 RPM for 20 to 30 minutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 3 PREPARATION OF DIMETHICONE CREAM CONTAINING CAPRYLIC/CAPRIC ACID TRIGLYCERIDE
A dimethicone cream composition containing caprylic/capric acid triglyceride was prepared as follows using the recipe set forth in Table 3 below.
Table 3 Dimethicone Composition Ingredients
INGREDIENTS %WEIGHT
Dimethicone 5.00
Caprylic/capric acid triglyceride 5.00
Glycerin 8.00
Citric acid (anhydrous) 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L-101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin B 1 0.50
Purified water 66.29
Total 100.00
Oil phase (phase A): Atmul 84, Amerchol L-101, cholesterol, Emulgade 1000,
Eumulgin Bl, capiylic/capric acid triglyceride (Croda Canada Ltd, Canada) and dimethicone are mixed at 72 to 78° C in a heated kettle.
Aqueous phase (phase B):
Purified water and glycerin were added into a reactor, mixed at 25 RPM, and heated. Citric acid and edetate were added, the temperature brought to
72 to 78° C and the ingredients mixed until uniform. Phase A, at 72 to78° C, was added to phase B, at 72 to 78° C, homogenized at 1000 RPM for 5 to 10 minutes
with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 minutes. The mixture was then cooled to 39 to 41° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35° C, with mixing at 20 RPM for 20 to 30 minutes. The mixture was then cooled to 24 to 28° C, with continued mixing at 20 RPM for 20 to 30 minutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 4 PREPARATION OF DIMETHICONE CREAM
CONTAINING A PROTEASE INHIBITOR
A dimethicone cream composition containing a protease inhibitor was prepared as follows using the recipe set forth in Table 4 below.
Table 4 Dimethicone Composition Ingredients
INGREDIENTS %WEIGHT
Dimethicone 5.00
Protease inhibitor 1.00
Glycerin 8.00
Citric acid (anhydrous). 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L-101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin Bl 0.50
Purified water 70.29
Total 100.00
Oil phase (phase A):
Atmul 84, Amerchol L-101, cholesterol, Emulgade 1000, Eumulgin Bl, and dimethicone were mixed at 72 to 78° C in a heated kettle. Aqueous phase (phase B):
Purified water and glycerin were added into a reactor, mixed at 25 RPM, and heated. Citric acid and edetate disodium were added, the temperature brought to 72 to 78° C and the ingredients mixed until uniform. Phase A, at 72 to 78° C, was added to phase B, at 72 to 78° C, and homogenized at 1000 RPM for 5 to 10 minutes with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 minutes. The mixture was then cooled to 39 to 41° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35° C, with mixing at 20 RPM for 20 to 30 minutes. Protease inhibitor was added and the mixture cooled to 24 to 28° C, with mixing at 20 RPM for 20 to 30 minutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 5
PREPARATION OF DIMETHICONE COMPOSITION
CONTAINING CAPRYLIC/CAPRIC ACID TRIGLYCERIDE AND A
PROTEASE INHIBITOR
A dimethicone composition containing caprylic/capric acid triglyceride and a protease inhibitor was prepared as follows using the recipe set forth in Table 5 below.
Table 5 Dimethicone Composition Ingredients
INGREDIENTS % WEIGHT
Dimethicone 5.00
Caprylic/capric triglyceride 5.00
Protease inhibitor 1.00
Glycerin 8.00
Citric acid anh. 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L-101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin B 1 0.50
Purified water 65.29
Total 100.00
Oil phase (phase A):
Atmul 84, Amerchol L-101, cholesterol, Emulgade 1000, Eumulgin Bl, caprylic/capric acid triglyceride and dimethicone were mixed at 72 to 78° C in a heated kettle. Aqueous phase (phase B):
Purified water and glycerin were added into a reactor, mixed at 25 RPM, and heated. Citric acid and edetate disodium were added, the temperature was brought to 72 to 78° C and the ingredients were mixed until uniform. Phase A, at 72 to 78° C, was added to phase B, at 72 to 78° C, homogenized at 1000 RPM for 5 to 10 minutes with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 minutes. The mixture was then cooled to 39 to 41° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35° C, with mixing at 20 RPM for 20 to 30 minutes. Protease inhibitor was added and the mixture cooled to 24 to 28° C, with mixing at 20 RPM for 20 to 30 mmutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 6
PREPARATION OF DIMETHICONE COMPOSITION
CONTAINING TRIACYLGLYCEROLS, SQUALENE AND A PROTEASE
INHIBITOR
A dimethicone composition containing triacylglycerols, squalene and a protease inhibitor was prepared as follows using the recipe set forth in Table 6 below.
Table 6 Dimethicone Composition Ingredients
INGREDIENTS % WEIGHT
Dimethicone 5.00
Caprylic/capric triglyceride 5.00
Squalene 5.00
Protease inhibitor 1.00
Glycerin 8.00
Citric acid anh. 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L- -101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin B 1 0.50
Purified water 60.29
Total 100.00
Oil phase (phase A):
Atmul 84, Amerchol L-101, cholesterol, Emulgade 1000, Eumulgin Bl, capyrlic/capric acid triglyceride, squalene (SUPRAENE, Robeco) and dimethicone were mixed at 72 to 78° C in a heated kettle. Aqueous phase (phase B):
Purified water and glycerin were added into a reactor, mixed at 25 RPM, and heated.Citric acid and edetate disodium were added, the temperature brought to 72 to 78° C and the ingredients mixed until uniform. Phase A, at 72 to 78° C, was added to phase B, at 72 to 78° C, homogenized at 1000 RPM for 5 to 10 minutes with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 minutes. The mixture was then cooled to 39 to 41° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35° C, with mixing at 20 RPM for 20 to 30 minutes. Protease inhibitor was added and the mixture cooled to 24 to 28° C, with mixing at 20 RPM for 20 to 30 minutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 7 PREPARATION OF DIMETHICONE CREAM COMPOSITION
CONTAINING CAPRYLIC/CAPRIC ACID TRIGLYCERIDE AND
SQUALENE
A dimethicone composition containing caprylic/capric acid triglyceride and squalene was prepared as follows using the recipe set forth in Table 7 below.
Table 7 Dimethicone Composition Ingredients
INGREDIENTS % WEIGHT
Dimethicone 5.00
Caprylic/capric triglyceride 5.00
Squalene (SUPRAEME) 5.00
Glycerin 8.00
Citric acid anh. 0.06
Edetate disodium 0.05
Atmul 84 4.00
Lanolin oil (Amerchol L-101) 3.00
Cholesterol 0.10
Emulgade 1000 8.00
Eumulgin Bl 0.50
Purified water 61.29
Total 100.00
Oil phase (phase A):
Atmul 84, Amerchol L-101, cholesterol, Emulgade 1000NI Eumulgin Bl, capyrlic/capric acid triglyceride, squalene and dimethicone were mixed at 72 to 78° C in a heated kettle. Aqueous phase (phase B):
Purified water and glycerin were added into a reactor, mixed at 25 RPM, and heated. Citric acid and edetate disodium were added, the temperature brought to 72 to 78° C and the ingredients mixed until uniform. Phase A, at 72 to 78° C, was added to phase B, at 72 to 78° C, homogenized at 1000 RPM for 5 to 10 minutes with mixing at 25 RPM. After homogenization, the mixture was cooled to 48 to 52° C with mixing at 28 RPM for 20 to 30 mmutes. The mixture was then cooled to 39 to 41°° C with mixing at 24 RPM for 20 to 30 minutes. The mixture was then cooled to 33 to 35° C, with mixing at 20 RPM for 20 to 30 minutes. The mixture is cooled to 24 to 28° C, with mixing at 20 RPM for 20 to
30 minutes. The dimethicone composition was transferred to a sterile, screw-cap jar and stored at room temperature until use.
EXAMPLE 8 TREATMENT OF INFLAMMATION WITH DIMETHICONE CREAM
COMPOSITION
Patients with eczema (inflammation) were treated with the dimethicone composition of Example 2. A thin film of the dimethicone composition was topically applied directly to the eczema several times a day for several days. The patients reported a decrease in the inflammation of the eczema. No adverse side effects of the dimethicone composition were reported.
A patient with a burned lower lip was treated with the dimethicone composition of Example 2. The dimethicone composition was topically applied directly to the burned lip three times a day for two weeks.
The patient reported a decrease in inflammation and healing of the lip. No adverse side effects of the dimethicone composition were reported.
A patient with a cut on one leg was treated with the dimethicone composition of Example 2. The dimethicone composition was topically applied directly to the cut twice a day for several days. The patient reported a decrease in inflammation and healing of the cut. No adverse side effects of the dimethicone composition were reported.
EXAMPLE 9
TREATMENT OF INFLAMMATION WITH DIMETHICONE CREAM
COMPOSITION CONTAINING CAPRYLIC/CAPRIC ACID
TRIGLYCERIDE
Patients with contact dermatitis were treated with the dimethicone composition of Example 3. A thin layer of the dimethicone
composition was topically applied directly to the rash several times a day for several days. The patients reported resolution of the inflammation. No adverse side effects of the dimethicone composition were reported.
A patient with actinic keratosis lesions was treated with the dimethicone composition of Example 3 twice a day for several weeks.
The patient reported a decrease in the inflammation of the lesion and drying, flaking-off and healing of the lesions. No adverse side effects of the dimethicone composition were reported.
Patients with bed sores were treated with the dimethicone composition of Example 3. A layer of the dimethicone composition was applied directly to the bed sore twice a day for a week. The patients reported a marked decrease in the inflammation of the bed sores and an improvement in healing of the bed sores. No adverse side effects of the dimethicone composition were reported.
EXAMPLE 10 EFFECT OF DIMETHICONE ON ELASTASE ACTIVITY
Although PMNs play an important role in killing infectious agents, they also contribute to the symptoms of inflammation by their release of proteolytic enzymes such as elastase.
To determine the effect of dimethicone on elastase activity, porcine pancreatic elastase (0.45 μg) in 900 μl of Tris-HCl buffer, pH 8.0, containing 0.5 M NaCl and 100 μg of BSA was incubated at 30° C in the presence of 0.2, 0.5, 0.7, 1, 1.6 and 2.0% dimethicone. After 15 minutes, 2 mM of the synthetic substrate N-Suc-AIa-Ala-Val-Ala-pNA was added, the incubation was continued for 15 minutes and the reaction was stopped with 100 μl of glacial acetic acid. Reaction product was measured spectrophotometricaπy at 410 nm.
As shown in Figure 1, 0.2 % of dimethicone was sufficient to significantly inhibit elastase activity. That increasing amounts of dimethicone did not equally inhibit elastase activity may result from the
low solubility of dimethicone in aqueous media. That is, as dimethicone is an oil, at high concentrations it may form micelles and is no longer available to interact with the elastase enzyme.
EXAMPLE 11
EFFECT OF DIMETHICONE ON PMN AND MACROPHAGE PHAGOCYTOSIS
PMNs are the first line of defense against invading pathogens and play a significant role during inflammation. In response to chemotatic factors, PMNs leave the circulation and invade the inflammed area where they recognize, phagocytize and kill the pathogens. Therefore, the effect of dimethicone on PMN phagocytosis was determined.
Blood was obtained from healthy human volunteers and PMNs were obtained by gradient centrifugation at 600 g for 30 minutes with Lympholyte-poly (Cedarlane, Hornby, Canada), followed by hypotonic lysis of contaminating erythrocytes. Cells were suspended in RPMI (Gibco, Burlington, Canada) supplemented with 10% fetal bovine serum (FBS). Final preparations consisted of greater than 95% PMNs as determined by Wright Giemsa staining having greater than 97% viability as determined by trypan blue exclusion.
Blood was obtained from healthy human volunteers and peripheral blood mononuclear leukocytes (hereinafter "PBMLs") were obtained by gradient centrifugation with Lympholyte-poly (Cedarlane, Hornby, Canada) at 600 g for 30 minutes at room temperature. The PBML fraction was collected and washed 3X with 10 ml of phosphate buffered saline (PBS) by centriugation. The cells were suspended in 5 ml of RPMI (Gibco) supplemented with 10% FBS (Hyclone). Viability was greater than 97% as determined by trypan blue exclusion. To assess the effect of dimethicone on phagocytosis, PMNs and PBMLs (2 X 106/ml) were incubated at 37° C in 5% C02, 95%
humidity in the presence of 0, 2.5 and 5% dimethicone. After 24 hours, viability was determined by trypan blue exclusion and the cells were washed 3X in PBS containing 2 M glucose, 1 mM MgCl2 and 1 mM CaCl2. The cell concentration was adjusted to 1 X 106 cells/ml and the cells were incubated with fluoresbrite carboxylate microspheres (1/10 dilution). After 30 minutes, the cells were washed, fixed in 2% paraformaldehyde and analyzed for microshpere ingestion using an XL flow Cytometer (Coulter). Data are expressed as percent (%) of phagocytosis. As shown in Figure 2 A, dimethicone stimulated PMN phagocytosis in six and inhibited PMN phagocytosis in two of the experiments. These data show that dimethicone modulates PMN phagocytosis and that the effect observed is dependent on the activated- state of the immune system of the donor. As shown in Figure 2B, dimethicone had no effect on macrophage phagocytosis.
EXAMPLE 12 EFFECT OF DIMETHICONE ON PBML PROLIFERATION
PBMLs were isolated as described in Example 11. The cells (2 X 105 cells/ml) were incubated in RPMI containing 10% FBS in the wells of 96- ell microtiter plates with 0, 10"5, 10"4, 10"3, 10"2, 10"1' 1 and 10X PHA (GIBCO, BURLINGTON, CANADA) at 37° C hours in the presence of 0 or 2.5% dimethicone (100% dimethicone). After 54 hours of incubation, 1 μCi of [3H]-thymidine was added to each well and the incubation was continued for 18 hours. Plates were harvested on Titertek filters and the radioactivity in each well was determined in a β-counter. Results are expressed in log CPM of incorporated [3H]-thymidine.
As shown in Figure 3, dimethicone inhibited PHA- stimulated mitogenic proliferation of PBMLs.
EXAMPLE 13 EFFECTS OF DIMETHICONE ON DERMAL SENSITIZATION IN MICE
Delayed type hypersensitivity (DTH) reactions in the skin represent an increasing cause of inflammatory dermatoses typically exemplified by allergic contact dermatitis (eczema). Skin sensitization in mice has been used as an animal model of atopic dermatitis. CD1 mice (20 g) were sensitized to oxazolone (OXA) under ketamine:xylazine anesthesia ( 0.1 ml/10 g, i.p.) by applying 100 μl of 5% solution of OXA (Sigma Chemicals, St-Louis) in acetone onto 2 cm area of the abdomen. Three days later, ear thickness was measured with a caliper, at the distal one third of the ear, and 50 μl of 5% OXA in acetone was applied on both faces of the right ear (challenge); the left ear served as control. Mice were distributed in 6 groups (10 animals per group) and treated with hydrocortisone (HC) and dimethicone (DM) according to the following table.
Treatment consisted of applying, twice daily, 25 μl of drug solution on both faces of the right ear. Ear thickness was measured every day and appearance of erythema was noted.
On days 10 and 17, mice were re-challenged by applying the OXA solution on the right ear, followed by the same treatment but only once daily for four days. Mice were sacrificed on day 21.
The mean increase of ear thickness (MIET) was determined by the formula below. Statistical analysis was performed using the Student's t test.
MIET = Mean thickness after challenge - Mean before challenge Number of mice treated
Results:
As shown in Figure 4, control animals had an MIET of 0.179 ± 0.05 mm (n=10). The ears showed acute inflammation as seen by erythema and swelling from 24 hours post challenge through the second challenge. Twice daily application of 1% hydrocortisone (positive control) suppressed by 74% (p < 0.00001) the MIET. Twice daily application of varying concentrations of dimethicone also significantly reduced MIET in a dose-dependent fashion. For acute inflammation, a concentration of 0.1% dimethicone had no significant effect. However, at concentrations of 1, 5 and 10%, significant reduction of inflammation (up to 55% inhibition) were observed (p < 0.003, 0.0014 and 0.0034 respectively). Both treatment (hydrocortisone and dimethicone) also reduced erythema of the ear.
To achieve chronic inflammation (swelling, redness and crust formation), mice were re-challenged at day 10 and 17. On day 14 and 21 respectively, the inflamed ear was 3 to 7 times thicker than the non-challenged ear. As shown in Figure 5 and 6, all doses of dimethicone inhibit significantly (up to 69%) the MIET. Topical application of dimethicone solution reduced redness, crust formation and ear swelling. Inhibition of inflammation by dimethicone was not as strong as hydrocortisone. However, hydrocortisone exerts a systemic effect as the mice treated with hydrocortisone showed a decrease of body weight (see Figure 7), probably due to immunosuppression.
All patents, patent applications and scientific articles mentioned herein are hereby incorporated by reference.
Modifications and variations of the present method will be obvious to those skilled in the art from the foregoing detailed description. Such modifications and variations are intended to come within the scope of the appended claims.
Claims (14)
1. A method for treating an inflammation of skin or a mucous membrane comprising administering a composition comprising dimethicone in a pharmaceutically acceptable carrier to the skin or mucous membrane of a mammal in an amount effective to reduce the inflammation.
2. The method of Claim 1 wherein the inflammation is eliminated.
3. The method of Claim 1 wherein the composition is administered topically.
4. The method of Claim 1 further comprising administering an anti-inflammatory agent.
5. The method of Claim 4 wherein the composition further comprises the anti-inflammatory agent.
6. The method of Claim 4 wherein the concentration of anti-inflammatory agent in the composition is insufficient to treat the inflammation when administered alone.
7. The method of Claim 4 wherein the anti- inflammatory agent is a nonsteroidal anti-inflammatory drug.
8. The method of Claim 4 wherein the anti- inflammatory agent is alpha- 1-antitrypsin.
9. The method of Claim 4 wherein the anti- inflammatory agent is hyaluronic acid or an analogue thereof.
10. The method of Claim 9 wherein the composition is administered in the bladder.
11. The method of Claim 1 further comprising administering an anti-infectious agent.
12. The method of Claim 11 wherein the composition further comprises the anti-infectious agent.
13. The method of Claim 1 further comprising administering an antihistamine.
14. The method of Claim 13 wherein the composition further comprises the antihististamine.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US24679200P | 2000-11-08 | 2000-11-08 | |
US60246792 | 2000-11-08 | ||
PCT/IB2001/002096 WO2002038160A1 (en) | 2000-11-08 | 2001-11-08 | Method for the treatment of inflammation |
Publications (1)
Publication Number | Publication Date |
---|---|
AU2002212606A1 true AU2002212606A1 (en) | 2002-05-21 |
Family
ID=22932223
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2002212606A Abandoned AU2002212606A1 (en) | 2000-11-08 | 2001-11-08 | Method for the treatment of inflammation |
Country Status (11)
Country | Link |
---|---|
US (1) | US20050101632A1 (en) |
EP (1) | EP1333839A1 (en) |
JP (1) | JP2004513149A (en) |
CN (1) | CN1561220A (en) |
AU (1) | AU2002212606A1 (en) |
BR (1) | BR0115215A (en) |
CA (1) | CA2428164A1 (en) |
IL (1) | IL155769A0 (en) |
MA (1) | MA25852A1 (en) |
MX (1) | MXPA03004017A (en) |
WO (1) | WO2002038160A1 (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7449203B2 (en) * | 2004-06-30 | 2008-11-11 | E-L Management Corporation | Cosmetic compositions and methods comprising Rhodiola rosea |
DE102005009515A1 (en) * | 2005-02-25 | 2006-09-07 | Exner, Heinrich, Dr. | A process for preparing a preparation of a DMSO-containing solid silicone oil emulsion for binding reactive oxygen compounds in the body of humans and animals |
DE102007007698A1 (en) | 2007-02-09 | 2008-08-21 | Exner, Heinrich, Dr. | Use of a highly emulsified silicone oil emulsion (HSE) for the manufacture of a medicament |
US9687517B2 (en) | 2007-12-20 | 2017-06-27 | Elc Management Llc | Methods and compositions for treating skin |
WO2009082511A1 (en) * | 2007-12-20 | 2009-07-02 | Elc Management Llc | Methods and compositions for treating skin |
US20100099766A1 (en) * | 2008-10-16 | 2010-04-22 | Novartis Ag | Topical NSAID compositions having sensate component |
US20110237674A1 (en) * | 2008-10-16 | 2011-09-29 | Novartis Ag | Topical nsaid compositions having sensate component |
CA2852210C (en) | 2010-10-26 | 2019-04-02 | Quinnova Pharmaceuticals, Inc. | Composition and method for treating wounds |
ES2746052T3 (en) * | 2011-06-28 | 2020-03-04 | Inhibrx Lp | Serpine fusion polypeptides and methods of use thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR175F (en) * | 1964-05-25 | 1900-01-01 | ||
US4847069A (en) * | 1987-10-22 | 1989-07-11 | The Procter & Gamble Company | Photoprotection compositions comprising sorbohydroxamic acid and an anti-inflammatory agent |
US5888523A (en) * | 1997-09-22 | 1999-03-30 | Biocontrol, Inc. | Topical non-steroidal anti-inflammatory drug composition |
US6262020B1 (en) * | 2000-02-15 | 2001-07-17 | Alphamed Pharmaceuticals Corp. | Topical wound therapeutic compositions |
-
2001
- 2001-11-08 AU AU2002212606A patent/AU2002212606A1/en not_active Abandoned
- 2001-11-08 EP EP01980821A patent/EP1333839A1/en not_active Withdrawn
- 2001-11-08 CA CA002428164A patent/CA2428164A1/en not_active Abandoned
- 2001-11-08 BR BR0115215-7A patent/BR0115215A/en not_active IP Right Cessation
- 2001-11-08 WO PCT/IB2001/002096 patent/WO2002038160A1/en not_active Application Discontinuation
- 2001-11-08 US US10/415,793 patent/US20050101632A1/en not_active Abandoned
- 2001-11-08 JP JP2002540743A patent/JP2004513149A/en not_active Withdrawn
- 2001-11-08 CN CNA018197442A patent/CN1561220A/en active Pending
- 2001-11-08 MX MXPA03004017A patent/MXPA03004017A/en unknown
- 2001-11-08 IL IL15576901A patent/IL155769A0/en unknown
-
2003
- 2003-05-05 MA MA27140A patent/MA25852A1/en unknown
Also Published As
Publication number | Publication date |
---|---|
MXPA03004017A (en) | 2004-02-12 |
BR0115215A (en) | 2003-12-30 |
CA2428164A1 (en) | 2002-05-16 |
IL155769A0 (en) | 2003-12-23 |
MA25852A1 (en) | 2003-07-01 |
WO2002038160A1 (en) | 2002-05-16 |
EP1333839A1 (en) | 2003-08-13 |
CN1561220A (en) | 2005-01-05 |
US20050101632A1 (en) | 2005-05-12 |
JP2004513149A (en) | 2004-04-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10881640B2 (en) | Topical pharmaceutical compositions for treatment of pilonidal sinus wounds | |
US6350785B2 (en) | Methods and compositions for topical treatment of damaged tissue using reactive oxygen metabolite production or release inhibitors | |
Avakian et al. | Toxic epidermal necrolysis: a review | |
US5658956A (en) | Bioadhesive-wound healing compositions and methods for preparing and using same | |
KR101018352B1 (en) | Composition of comprising bee-venoms for treating acne | |
EP0462964B1 (en) | Topical compositions containing aliphatic amines for the treatment of skin diseases | |
EP0754052A1 (en) | Antiviral wound healing composition containing a pyruvate, an antioxidant, a mixture of fatty acids and an antiviral compound | |
EP1077066A1 (en) | Preventives/remedies for skin diseases | |
WO1996014085A1 (en) | External preparation for skin protection | |
US4256763A (en) | Treatment of herpes simplex infections and acne | |
US20040171561A1 (en) | Topical formulations for treatment of rosacea | |
US7655255B2 (en) | Topical composition for transdermal administration | |
RU2401100C2 (en) | Acid and buffer skin care compositions containing nicotinamide and absorbing agent | |
US20050101632A1 (en) | Method for the treatment of inflammation | |
US5667790A (en) | Aluminum chlorhydrate as a treatment for acne and rosacea | |
US4520132A (en) | Use of undecylenic acid to treat herpes labialis | |
NL9300065A (en) | COMPOSITION FOR ACCELERATING WOUND HEALING. | |
CA1317884C (en) | Treatment of skin diseases and tumors | |
AU2240295A (en) | Antiviral wound healing composition containing a pyruvate, an antioxidant, a mixture of fatty acids and an antiviral compound | |
CA2392544A1 (en) | Natural therapeutic composition for the treatment of wounds and sores |