Composition & use as analgesic, anti-inflammatory, wound healing agent, for treatment of heart conditions, assessment of heart function & tissue & cell protection & healing & reperfusion, mood disorders & symptoms & sequelae of menopause & for inducing unconsciousness, sleep & anesthesia

• US 20030181353A1
• Filed: 01/21/2003
• Published: 09/25/2003
• Est. Priority Date: 08/03/1998
• Status: Abandoned Application

• Current Assignee: Jonathan W. Nyce
• Original Assignee: Jonathan W. Nyce
• Inventors: Nyce, Jonathan W.
• Application Number:
  US10/349,219
• Publication Number:
  US 20030181353A1
• Time in Patent Office: Days
• US Class Current: 514/1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Composition and formulations comprise a brain, heart, lung and/or vascular system protecting amount of a first agent such as folinic acid, pharmaceutically acceptable salts thereof or mixtures thereof and a carrier, and optionally a second agent such as analgesics, heart medicines, anti-inflammatory agents, soporifics, muscle relaxants, anti-pyretic agents, anti-fibrillation agents, heart, brain, lung and vascular drugs, anxiolytic agents, mood controlling agents, and many others. The products are suitable for the treatment of previous mood disorders, symptoms and sequelae of menopause, pain, inflammation, insomnia, restless sleep, trauma, surgery, burns, conditions and diseases which bring these symptoms, ischemia, Supra Ventricular Tachycardia (SVT), heart conditions and heart failure, Acute Respiratory Distress Syndrome (ARDS), COPD, allergic rhinitis, and other conditions, and for reducing the number and severity of heart attacks, as well as for alleviating other diseases associated with the heart, and more generally, for the assessment of heart function. An edible product is prepared with the agent of the invention.

Claims

95. A pharmaceutical composition, comprising a pharmaceutically or veterinarily acceptable carrier and an amount of a first agent effective as an anti-pyretic, analgesic, unconsciousness inducer or anesthetic, or as an aggressive behavior or neutrophil function regulator, or as a protector or inducer of reperfusion of ischemic or stroke afflicted organs, tissue, cell or vasculature, or for alleviating chronic bronchitis, COPD, allergic rhinitis, auto-immune diseases, wounds, burns, inflammation, sequelae of menopause, bed sores or heart conditions, or for assessing heart or cardiovascular function, the first agent being selected from folinic acid, its physiologically acceptable salts or mixtures thereof.

96. The composition of claim 95, further comprising a second agent selected from analgesics, anti-pre-menstrual syndrome (PMS) agents, anti-menopausal agents, anti-aging agents, anti-anxiolytic agents, mood controlling agents, anti-depressants, anti-bipolar mood disorder agents, anti-schizophrenic agents, anti-cancer agents, aggression controlling agents, anti-attention deficit disorder agents, anti-delirium agents, anti-compulsive obsessive disorder (COD) agents, anti-seizure agents, alkaloids, blood pressure controlling agents, hormones, anti-inflammatory agents, muscle relaxants, steroids, soporific agents, anti-ischemic agents, anti-arrhythmic agents, contraceptives, vitamins, minerals, tranquilizers, neurotransmitter regulating agents, wound healing agents, anti-angiogenic agents, cytokines, growth factors, anti-metastatic agents, antacids, anti-histaminic agents, anti-bacterial agents, anti-viral agents, anti-gas agents, appetite suppressants, anti-wasting disorder agents, anti-bulimic agents, anti-anorexia nervosa agents, brain injury agents, heart attack agents, adenosine, adenosine releasing agents and adenosine receptor stimulating agents, sun screens, emollients, skin temperature lowering agents, radioactive phosphorescent and fluorescent contrast diagnostic and imaging agents, libido altering agents, bile acids, laxatives, anti-diarrheic agents, skin renewal agents or hair growth agents.

97. The composition of claim 95, wherein the first agent is provided in an amount effective for stabilizing or regulating heart activity, for alleviating or controlling pain or inflammation, for preventing or treating viral or microbial infection, skin lacerations, organ or tissue trauma, burns, restless sleep, stroke, heart failure, arrythmias, heart fibrillation, SVT, RDS, chronic bronchitis, COPD, allergic rhinitis or auto-immune disease or intensity, frequency or severity of heart attacks or strokes, or for inducing unconsciousness, α

-wave sleep or anesthesia.

98. The composition of claim 97, wherein the pain or inflammation is associated with bed sores, burns, trauma, Crohn'"'"'s disease, ulcerative colitis (UC), surgery or arthritis.

99. The composition of claim 97, wherein the pain or inflammation is associated with head aches, ear aches, head or peripheral body injury, pre- and post-surgical pain, back pain, child birth pain, pre- and post-partum pain, sport injuries, exercise or over-exertion pain, intake of steroids, osteoporosis, trauma, surgery, burns, wounds, sores, chronic bronchitis, chronic obstructive pulmonary disease (COPD), allergic rhinitis, inflammatory bowel disease (IBD) or autoimmune disease.

100. The composition of claim 95, further comprising a surfactant selected from surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant protein fragments thereof, non-dipalmitoyl disaturated phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholin, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate, artificial lamellar bodies vehicles for surfactant components, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitic acid, non-ionic ethylene and/or propylene oxide block copolymers, polyoxypropylene, polyoxyethylene, poly (vinyl amine) with dextran and/or alkanoyl side chains, Brij 35®

, Triton X-100®

, ALEC®

, Exosurf®

, Survant®

or Atovaquone®

.

101. The formulation of claim 95, further comprising anti-oxidants, flavoring agents, volatile oils, buffering agents, dispersants, propellants, preservatives or surfactants.

102. The formulation of claim 100, wherein the formulation is selected from oral, intrabuccal, intrapulmonary, rectal, intrauterine, intradermal, topical, dermal, parenteral, intratumor, intracranial, buccal, sublingual, nasal, intramuscular, subcutaneous, intravascular, intrathecal, inhalable, transdermal, intraarticular, intracavitary, implantable, transdermal, iontophoretic, intraocular, ophthalmic, vaginal, intraarticular, otical, intravenous, intramuscular, intraglandular, intraorgan, intralymphatic, implantable, slow or sustained release or enteric coating formulations.

103. The composition of claim 102, which is an oral formulation selected from the group consisting of capsules, cachets, lozenges, tablets, powder, granules, solutions, suspensions and emulsions.

104. The oral formulation of claim 103, wherein the solutions or suspensions comprise aqueous or non-aqueous liquid solutions or suspensions, and the emulsions comprise oil-in-water or water-in-oil emulsions.

105. The oral formulation of claim 102, which is a buccal or sub-lingual formulation selected from lozenges that may further comprise a flavoring agent selected from sucrose, acacia or tragacanth;

or pastilles that may further comprise an inert base selected from gelatin, glycerin, sucrose or acacia.

106. The oral formulation of claim 103, further comprising an enteric coating.

107. The composition of claim 102, which is a parenteral formulation selected from injectable solutions, suspensions or emulsions that may further comprise anti-oxidants, buffers, bacteriostatic agents or solutes which render the solution or suspension isotonic with blood.

108. The parenteral formulation of claim 107, wherein the solutions, suspensions or emulsions are selected from sterile aqueous or non-aqueous injection solutions, suspensions or emulsion that may further comprise suspending agents or thickening agents.

109. A sterile ampoule or vial, comprising the parenteral formulation of claim 107.

110. The composition of claim 95, which is in bulk, or in single- or multi-unit dose form.

111. The composition of claim 95, which is freeze-dried or lyophilized.

112. The composition of claim 103, which is a topical formulation selected from ointments, creams, lotions, pastes, gels, sprays, aerosols or oils.

114. The topical formulation of claim 112, wherein the carrier is selected from vaseline, lanoline, polyethylene glycols, alcohols or transdermal transport enhancers.

115. The composition of claim 112, which is a transdermal formulation.

116. The transdermal formulation of claim 115, comprising a solution, suspension or emulsion of the first agent, which may further comprise a buffer and one or more second agent(s).

117. A transdermal delivery device, for delivery of the formulation of claim 115.

118. A transdermal delivery device, comprising the formulation of claim 115, which may comprise a patch.

119. The formulation of claim 103, which is an inhalable, nasal, respirable or intrapulmonary formulation.

120. The formulation of claim 119, which is an aerosol comprising liquid or solid particles that may further comprise an agent selected from preservatives, antioxidants, flavoring agents, volatile oils, buffering agents, dispersants or surfactants.

121. The formulation of claim 119, comprising a powder or liquid formulation of respirable, nasal, intrapulmonary or inhalable particles about 0.5 to about 10 μ

m in size or about 10 to about 500 μ

m in size.

122. The formulation of claim 121, comprising particles about 0.5 up to about 5 μ

m in size.

123. The formulation of claim 120, which is an aerosol powder comprising solid particles about 0.5 to about 10 μ

m in size or about 10 to about 500 μ

m in size.

124. The formulation of claim 120, which is a liquid aerosol of particles about 0.5 to about 10 μ

m in size or about 10 to about 500 μ

m in size.

125. The formulation of claim 119, provided in a capsule(s) or cartridge(s).

126. The composition of claim 102, wherein the carrier comprises a hydrophobic carrier.

127. A delivery device, for nasal, inhalation, respiratory or intrapulmonary delivery of the formulation of claim 119.

128. A delivery device for nasal, respiratory, inhalation or intrapulmonary delivery, comprising the formulation of claim 119.

129. The device of claim 127, comprising an inhalator.

130. The device of claim 129, wherein the inhalator comprises a nebulizer or insufflator.

131. The delivery device of claim 129, comprising a pressurized inhalator.

132. The delivery device of claim 127, comprising a device that delivers a pre-measured dose(es) of the formulation.

133. A kit comprising a delivery device for nasal, inhalation, respiratory or intrapulmonary delivery device, in a separate container the agent of claim 95, and instructions for preparation of a nasal, inhalation, respiratory or intrapulmonary formulation and for its delivery.

134. The kit of claim 133, wherein the device comprises an inhalator.

135. The kit of claim 134, wherein the inhalator comprises a nebulizer or insufflator that may receive, and be operated to pierce or open, a capsule or cartridge, and the kit further comprises a piercable or openable capsule or cartridge with solid or liquid particles of the composition.

136. The kit of claim 133, wherein the delivery device comprises a pressurized inhalator, and the instructions provided are for the preparation of a formulation comprising a suspension or solution in an aqueous or non-aqueous liquid or an oil-in-water or water-in-oil emulsion.

137. A kit for nasal, inhalation, respiratory or intrapulmonary delivery, comprising a device for nasal, inhalation, respiratory or intrapulmonary delivery, in a separate container the formulation of claim 119, and instructions for its use.

138. The kit of claim 133, further comprising in a separate container a surfactant.

139. The kit of claim 138, wherein the surfactant is selected from surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant protein and active fragments thereof, non-dipalmitoyl disaturated phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholin, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate, artificial lamellar bodies vehicles for surfactant components, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitic acid, non-ionic ethylene and/or propylene oxide block copolymers, polyoxypropylene, polyoxyethylene, poly (vinyl amine) with dextran and/or alkanoyl side chains, Brij 35, Triton X-100, ALEC, Exosurf, Survant or Atovaquone.

140. The composition of claim 103, which comprises a suppository(ies).

141. The composition of claim 103, which comprises an implant(s).

142. The composition of claim 102, which comprises a slow or sustained release formulation.

143. The composition of claim 103, which comprises an ophthalmic formulation.

144. The composition of claim 103, which comprises an otical formulation.

145. The composition of claim 103, which comprises a vaginal formulation selected from creams, gels, suppositories or implants.

146. The composition of claim 96, comprising a carrier, a first agent(s), and a second agent(s) selected from analgesic agents, anti-inflammatory agents, muscle relaxant agents, sleep inducing agents, anti-anxiolytic agents, diuretics, mood altering agents, vitamins, minerals, proteins, or hormonal agents.

147. The composition of claim 146, wherein the second agent(s) comprise(s) a mood regulating agent(s).

148. The composition of claim 146, wherein the second agent(s) comprise(s) a diuretic(s).

149. The composition of claim 146, wherein the second agent(s) comprise(s) vitamins and/or minerals.

150. The composition of claim 146, wherein the second agent(s) comprise(s) an anti-anxiolytic agent(s).

151. The composition of claim 146, wherein the second agent(s) comprise(s) one or more analgesic and/or anti-inflammatory agent(s).

152. The composition of claim 146, wherein the second agent(s) comprise(s) one or more hormonal agent(s).

153. The composition of claim 146, comprising the first agent(s), a hormone(s) having estrogen and progesterone activity, a diuretic(s), an analgesic(s) or an anti-inflammatory agent(s).

154. The composition of claim 115, which comprises an iontophoretic transdermal formulation further comprising an iontophoretic transport promoting agent(s), wherein the carrier is selected from solutions, suspensions or emulsions that comprise an aqueous or alcoholic solution or suspension, an oily solution or suspension or an oil-in-water or water-in-oil emulsion.

155. An iontophoretic delivery device, for delivery of the formulation of claim 154.

156. An iontophoretic device, comprising the formulation of claim 154.

157. An implantable capsule or cartridge, comprising the transdermal formulation of claim 115.

158. A transdermal delivery kit comprising, in separate containers,

a transdermal delivery device;

the agent of the formulation of claim 115;

and

instructions for preparing the formulation and for its use.

159. The formulation of claim 126, wherein the hydrophobic carrier is selected from lipid vesicles or particles.

160. The formulation of claim 159, wherein the vesicles comprise liposomes, or the particles comprise microcrystals.

161. The composition of claim 160, wherein the liposomes comprise the first agent, and optionally one or more second agent(s) selected from analgesics, anti-pre-menstrual syndrome (PMS) agents, anti-menopausal agents, anti-aging agents, anti-anxiolytic agents, mood controlling agents, anti-depressants, anti-bipolar mood disorder agents, anti-schizophrenic agents, anti-cancer agents, aggression controlling agents, anti-attention deficit disorder agents, anti-delirium agents, anti-compulsive obsessive disorder (COD) agents, anti-seizure agents, alkaloids, blood pressure controlling agents, hormones, anti-inflammatory agents, muscle relaxants, steroids, soporific agents, anti-ischemic agents, anti-arrhythmic agents, contraceptives, vitamins, minerals, tranquilizers, neurotransmitter regulating agents, wound healing agents, anti-angiogenic agents, cytokines, growth factors, anti-metastatic agents, antacids, anti-histaminic agents, anti-bacterial agents, anti-viral agents, anti-gas agents, appetite suppressants, anti-wasting disorder agents, anti-bulimic agents, anti-anorexia nervosa agents, brain injury agents, heart attack agents, adenosine, adenosine releasing agents and adenosine receptor stimulating agents, sun screens, emollients, skin temperature lowering agents, radioactive phosphorescent and fluorescent contrast diagnostic and imaging agents, libido altering agents, bile acids, laxatives, anti-diarrheic agents;

skin renewal agents or hair growth agents.

162. A method for inducing anti-pyresis, unconsciousness or anesthesia, or for regulating neutrophil function, prophylactically or therapeutically protecting or inducing reperfusion of ischemic or stroke afflicted endogenous and in-transplantation organs, tissues, cells or vasculature, or for alleviating chronic bronchitis, COPD, allergic rhinitis, auto-immune disease, bed sores, wounds, burns, inflammation, sequelae of menopause, heart conditions, or for assessing heart or cardiovascular function, comprising administering to a subject in need of treatment the pharmaceutical composition of claim 95, comprising an anti-pyretic, analgesic, unconsciousness inducing or anesthetic, an aggressive behavior or neutrophil function regulating, a reperfusion of ischemic or stroke afflicted organ, tissue, cell or vasculature protective or inducing, a chronic bronchitis, COPD, allergic rhinitis, auto-immune diseases, wound, burn, inflammation, sequelae of menopause, bed sores, or heart condition alleviating, or a heart or cardiovascular function assessing effective amount of the first agent of claim 95.

163. The method of claim 162, wherein the first agent is administered in an amount of about 1 to about 1,000 mg/kg body weight.

164. The method of claim 162, for stabilizing or regulating heart activity, for preventing or treating inflammation, sores, burns, trauma, Crohn'"'"'s disease, ulcerative colitis (UC), surgery, arthritis, viral or microbial infection, skin lacerations, organ or tissue trauma, burns, restless sleep;

stroke, heart failure, arrythmias, heart fibrillation, SVT, RDS, chronic bronchitis, COPD, allergic rhinitis, the intensity, frequency or severity of heart attacks or stroke or auto-immune disease, or for inducing unconsciousness, α

-wave sleep or anesthesia.

165. The method of claim 162, for preventing or treating arthritis, head aches, ear aches, body injury, pre- and post-surgical pain, back pain, pain associated with child birth, pre- and postpartum pain, sport injuries, muscle pain associated with exercise or over-exertion, pain associated with intake of steroids, osteoporosis, trauma, surgery, burns, wounds, chronic bronchitis, chronic obstructive pulmonary disease (COPI)), allergic rhinitis, inflammatory bowel disease (IBD) or autoimmune disease.

166. The method of claim 162, further comprising administering to the subject a second agent selected from analgesics, anti-pre-menstrual syndrome agents, anti-menopausal agents, anti-aging agents, anti-anxiolytic agents, mood controlling agents, anti-depressants, anti-bipolar disorder agents, anti-schizophrenic agents, anti-cancer agents, alkaloids, blood pressure controlling agents, hormonal agents, anti-inflammatory agents, muscle relaxants, steroids, soporific agents, anti-ischemic agents, anti-arrhythmic agents, contraceptives, vitamins, minerals, tranquilizers, soporifics, appetite suppressants, neurotransmitter regulating agents, wound healing agents, anti-angiogenic agents, cytokines, growth factors, anti-metastatic agents, antacids, anti-histaminic agents, anti-bacterial agents, anti-viral agents, anti-gas agents, appetite suppressants, anti-wasting disorder agents, anti-bulimic agents, anti-anorexia nervosa agents, brain injury agents, heart medicines, adenosine, adenosine releasing agents, adenosine metabolism inhibitors, or adenosine receptor stimulating agents, sun screens, emollients, skin temperature lowering agents, radioactive phosphorescent and fluorescent contrast diagnostic and imaging agents, libido altering agents, bile acids, laxatives, anti-diarrheic agents, skin renewal agents or hair growth agents.

167. The method of claim 166, wherein the second agent comprises an analgesic, anti-inflammatory, mood regulating agent, muscle relaxant or sleep regulating agent(s).

168. The method of claim 162, wherein the composition is administered systemically or topically.

169. The method of claim 168, wherein the composition is administered buccally, sublingually, dermally, intraocularly, subcutaneously, intradermally, intramuscularly, intravenously, intraarticularly, intrapulmonarily, rectally, intrauterinely, parenterally, intratumorly, intracranially, nasally, intravascularly, intrathecally, transdermally, intracavitarily, iontophoretically, ophthalmic, vaginally, otically, intraglandularly, intraorgan or lymphatically, or by inhalation or implantation, or into the respiration.

170. The method of claim 169, wherein the composition is administered orally as a formulation selected from capsules, cachets, lozenges, tablets, powder, granules, solutions, suspensions or emulsions.

171. The method of claim 170, wherein the oral formulation further comprises an enteric coating.

172. The method of claim 169, wherein the composition is administered buccally or sub-lingually in the form of lozenges that may further comprise a flavoring agent(s) selected from sucrose, acacia or tragacanth;

or pastilles that may further comprise an inert base selected from gelatin, glycerin, sucrose or acacia.

173. The method of claim 169, wherein the composition is administered parenterally in the form of an injectable solution, suspension or emulsion, which may further comprise antioxidants, buffers, bacteriostatic agents, or solutes that render the solution, suspension or emulsion isotonic with blood.

174. The method of claim 162, wherein the composition is freeze-dried or lyophilized;

and the method further comprises adding a sterile liquid or solid carrier prior to use.

175. The method of claim 169, wherein the composition is administered topically as an ointment, cream, lotion, paste, gel, spray, aerosol or oil that may further comprise vaseline, lanoline, polyethylene glycols, alcohol or trans-dermal transport enhancers.

176. The method of claim 169, wherein the composition is administered transdermally from a patch.

177. The method of claim 162, further comprising administering a surfactant selected from surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant protein fragments thereof, non-dipalmitoyl disaturated phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholin, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate, artificial lamellar bodies vehicles for surfactant components, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitic acid, non-ionic ethylene and/or propylene oxide block copolymers, polyoxypropylene, polyoxyethylene, poly (vinyl amine) with dextran and/or alkanoyl side chains, Brij 35®

, Triton X-100®

, ALEC®

, Exosurf®

, Survant®

or Atovaquone®

.

178. The method of claim 177, wherein the first agent and the surfactant are administered in one composition.

179. The method of claim 169, wherein the composition is administered by inhalation, respiration, nasaly or intrapulmonarily.

180. The method of claim 179, wherein the composition is administered as an inhalable, respirable, nasal or intrapulmonary formulation comprising an aerosol of liquid solid powdered particles.

181. The method of claim 162, wherein the composition further comprises preservatives, antioxidants, flavoring agents, volatile oils, buffering agents, dispersants or surfactants.

182. The method of claim 180, wherein the aerosol comprises particles about 0.5 to about 10 μ

m in size or about 10 to about 500 μ

m in size.

183. The method of claim 180, wherein the aerosol comprises particles about 0.5 to about 5 μ

m in size.

184. The method of claim 169, wherein the composition is administered vaginally or rectally.

185. The method of claim 169, wherein the composition is administered ophthalmically or otically.

186. The method of claim 169, wherein the composition is administered intraarticularly.

187. The method of claim 162, wherein the composition further comprises other therapeutic agent(s), a preservative(s), an anti-oxidant(S), a flavoring agent(s), a volatile oil(s), a buffering agent(s), a dispersant(s) or surfactant(s).

188. The method of claim 162, wherein the subject is a human or a non-human animal.

189. The method of claim 162, for prophylaxis or treatment of a disease or condition associated with burns, trauma, inflammation, pain, surgery, viral infection, microbial infection, ischemia, congestion, inflammation, auto-immune disease, menopause, prolonged bed rest, surgery, bulimia, anorexia nervosa, or wasting disorder.

190. The method of claim 189, wherein the disease or condition is also associated with sleeplessness, cancer or a mood disorder.

191. The method of claim 190, wherein the patient is prone to, or is afflicted with, depression, bipolar disease, schizophrenia, over-aggressiveness, attention deficit disorder (ADD), delusions, compulsive obsessive disorder (COD) or delirium.

192. The method of claim 189, wherein the patient is subject to an operation, traumatic body injury, chronic pain or cancer.

193. The method of claim 160, wherein the first agent is administered in an amount of about 1 to about 1,000 mg/kg body weight of the subject.

194. The method of claim 162, further comprising administering to the subject a second agent selected from analgesics, anti-pre-menstrual syndrome agents, anti-menopausal agents, anti-aging agents, anti-anxiolytic agents, other mood disorder regulating agents, anti-depressants, anti-bipolar mood disorder agents, anti-schizophrenic agents, anti-attention deficit disorder (ADD) agents, anti-cancer agents, alkaloids, blood pressure controlling agents, hormones, anti-inflammatory agents, muscle relaxants, steroids, soporific agents, anti-ischemic agents, anti-arrhythmic agents, contraceptives, vitamins, minerals, tranquilizers, neurotransmitter regulating agents, wound healing agents, hormonal agents, anti-arthritic agents, anti-compulsive obsessive disorder (COD) agents, aggression level lowering agents, anti-angiogenic agents, cytokines, growth factors, anti-metastatic agents, antacids, anti-histaminic agents, anti-bacterial agents, anti-viral agents, anti-gas agents, appetite suppressants or stimulants, anti-wasting disorder agents, anti-bulimic agents, anti-anorexia nervosa agents, brain injury agents, heart attack agents, adenosine, adenosine releasing agents, adenosine receptor stimulating agents, sun screens, emollients, skin temperature lowering agents, radioactive phosphorescent or fluorescent contrast diagnostic or imaging agents, libido altering agents, bile acids, laxatives, anti-diarrheic agents, skin renewal agents or hair growth agents.

195. The method of claim 194, wherein the composition comprises the first agent(s), a hormone(s) having estrogen or progesterone activity, a diuretic(s) and an analgesic or anti-inflammatory agent(s).

196. A foodstuff, comprising the composition of claim 95, and other edible ingredients.

197. The foodstuff of claim 196, selected from milk, juices, cereals, energy bars, chewing gum, cookies, candy, crackers, drinks, cakes, pasta, and salad dressing, vegetables, meats or fruits.

198. The product of claim 197, wherein the foodstuff comprises infant formula, milk, baby food, cookies, or crackers.

199. A kit for preparation of a foodstuff, comprising in separate containers

the first agent of claim 95;

foodstuff ingredients; and

instructions for combining the foodstuff ingredients with the first agent and other non-provided ingredients, and for preparation of the foodstuff.

200. The kit of claim 199, wherein the ingredients and the first agent are provided in a foodstuff composition.

201. The kit of claim 199, further comprising in a separate container a second agent selected from analgesics, anti-pre-menstrual syndrome agents, anti-menopausal agents, anti-aging agents, anti-anxiolytic agents, other mood controlling agents, anti-depressants, anti-bipolar mood disorder agents, anti-schizophrenic agents, anti-cancer agents, aggression controlling agents, anti-attention deficit disorder agents, anti-delirium agents, anti-compulsive obsessive disorder agents, anti-aggression agents, anti-seizure agents, alkaloids, blood pressure controlling agents, hormones, anti-inflammatory agents, muscle relaxants, steroids, soporific agents, anti-ischemic agents, anti-arrhythmic agents, contraceptives, vitamins, hormonal agents, minerals, tranquilizers, neurotransmitter regulating agents, wound healing agents, anti-angiogenic agents, cytokines, growth factors, anti-metastatic agents, antacids, anti-histaminic agents, anti-bacterial agents, anti-viral agents, anti-gas agents, appetite suppressants, anti-wasting disorder agents, anti-bulimic agents, anti-anorexia nervosa agents, brain injury agents, heart attack agents, adenosine, adenosine releasing agents and adenosine receptor stimulating agents, sun screens, emollients, skin temperature lowering agents, radioactive phosphorescent and fluorescent contrast diagnostic and imaging agents, libido altering agents, bile acids, laxatives, anti-diarrheic agents, skin renewal agents or hair growth agents.

202. The kit of claim 199, further comprising in a separate container a surfactant selected from surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant protein fragments thereof, non-dipalmitoyl disaturated phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholin, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate, artificial lamellar bodies vehicles for surfactant components, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitic acid, non-ionic ethylene and/or propylene oxide block copolymers, polyoxypropylene, polyoxyethylene, poly (vinyl amine) with dextran and/or alkanoyl side chains, Brij 35®

, Triton X-100®

, ALEC®

, Exosurf®

, Survant®

or Atovaquone®

.

100-1. The composition of claim 95, wherein the carrier comprises a liquid or solid carrier;

and the composition comprise4s a systemic or topical formulation.