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US 20150.064285A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0064285 A1 LIU et al. (43) Pub. Date: Mar. 5, 2015 (54) SLOW RELEASE MAGNESIUM Publication Classification COMPOSITION AND USES THEREOF (51) Int. Cl. (71) Applicant: Magceutics, Inc., Hayward, CA (US) A633/06 (2006.01) A63/94 (2006.01) (72) Inventors: Guosong LIU, East Palo Alto, CA (US); A63L/98 (2006.01) Fei Mao, Fremont, CA (US) A63L/9I (2006.01) A633/14 (2006.01) (73) Assignee: Magceutics, Inc., Hayward, CA (US) (52) U.S. Cl. CPC ............... A61 K33/06 (2013.01); A61 K3I/191 (2013.01); A61 K33/14 (2013.01); A61 K (21) Appl. No.: 14/222,357 31/198 (2013.01); A61 K31/194 (2013.01) USPC ........... 424/681; 424/682: 514/557: 514/561; (22) Filed: Mar. 21, 2014 5147574. Related U.S. Application Data (57) ABSTRACT (63) Continuation of application No. 13/736,679, filed on The present invention provides compositions that contain Jan. 8, 2013, now Pat. No. 8,734.855, which is a con- magnesium and threonate, or a threonate precursor molecule, tinuation of application No. 12, 829 361 filed on Jul.1 formulated for extended or modified release to provide physi 2010, now Pat No. 8377,473 s- Y -us s ological concentrations over a desired time period. The s • L vs. 8 Y-s- s - • extended release or modified release form is particularly use (60) Provisional application No. 61/222,420, filed on Jul. 1, ful in providing Mg to a Subject while avoiding adverse side 2009. effects such as diarrhea. Patent Application Publication Mar. 5, 2015 Sheet 1 of 6 US 2015/0064285 A1 (%) eeu-LeO Patent Application Publication Mar. 5, 2015 Sheet 3 of 6 US 2015/0064285 A1 (SÁep)?uu?L 0|| 00|| (%)(6WIV Patent Application Publication Mar. 5, 2015 Sheet 4 of 6 US 2015/0064285 A1 3 St.C S.r 3.O & 9 CD 8 cus ooo- 3. S CD CD go 8 9 O OO O CO O O C O O O 9 o co V CN n (%)|e/\/\InSO 3AIA N - O Cd C s vS. SeO P O 1 a CD CD CD 3. c CD d S E N. H. 3 Cd Cd Cd Cd Cd C CO cC V S w (%)|eMIAunS Patent Application Publication Mar. 5, 2015 Sheet 5 of 6 US 2015/0064285 A1 3 3 8 3 S. O O O s & co s S (%)|eAIAunS s S 3 3 S. (6) publeM Apo Patent Application Publication Mar. 5, 2015 Sheet 6 of 6 US 2015/0064285 A1 S. (%) peSeele J 5W US 2015/0064285 A1 Mar. 5, 2015 SLOW RELEASE MAGNESUM Oct. 25; 298:789-91). During normal aging, memory decline COMPOSITION AND USES THEREOF also correlates with synaptic loss (Terry R D, Masliah E. Salmon D. P. Butters N, DeTeresa R, Hill R. Hansen LA, RELATED APPLICATIONS Katzman R. Ann Neurol. 1991 October:30:572-80). Interest ingly, brain magnesium contents in AD patients (Andrasi E. 0001. This application claims the benefit of U.S. Provi Pali N, Molnar Z, Kosel S. J Alzheimers Dis. 2005 August: sional Application No. 61/222,420, filed Jul. 1, 2009, which is 7:273-84: Cilliler A E, Ozturk S, Ozbakir S. Gerontology. incorporated by reference herein in its entirety. 2007 Nov. 8: 53:419-22) are lower than normal subjects. Elevation of brain magnesium might be beneficial for preven BACKGROUND OF THE INVENTION tion of synapse loss and amelioration of memory decline 0002 Magnesium is the fourth most abundant mineral in during aging and the pathological processes of AD. the human body and plays multiple roles in maintaining good 0005. Despite the important physiological role of magne health. At the molecular level, magnesium is a cofactor for sium, people may not consume enough magnesium in their over 300 enzymes responsible for some of the most important diets. In a national sample of the United States, the mean biological activities in mammals, including humans. In living value of daily magnesium between the ages of 20-30 is ~300 cells, magnesium is involved in the homeostasis of other mg for white and ~250 mg for black males. This daily intake minerals, such as sodium, potassium and calcium, and the declines, at ages above 70 years, to ~200 mg as a result of formation, transfer, Storage and utilization of adenosine triph reduced food consumption. On the other hand, the recom osphate (ATP), a principal source of energy in living cells. In mended daily allowance (RDA) for males is 420 mg/day. the human body, magnesium is involved in the maintenance Therefore, it is likely that the majority of the American male of normal muscle and nerve function, heart rhythm, bone population has magnesium deficit, particularly during aging. strength, and immune system health. Magnesium is also A similar degree of deficit also occurs in American female involved in the regulation of blood sugar levels and the pro population (Ford ES, Mokdad A H.J. Nutr. 2003 September; motion of normal blood pressure. 133:2879-82). Based on this study, most of the American 0003 Magnesium deficit has been associated with several population needs to Supplement their diet with an additional diseases, including hypertension, atherosclerosis, arrhyth ~200 mg/day of magnesium. Interestingly, magnesium con mia, diabetes, and metabolic syndromes. In addition, magne tained in food provides relatively high absorption rate mag sium deficit accelerates cell-aging processes (Killilea D. W. nesium (~50%), which may suggest that ~100 mg/day mag Ames B N. Magnesium deficiency accelerates cellular senes nesium remains needed to be absorbed into the body. In cence in cultured human fibroblasts. Proc Natl AcadSci USA. general, most commercially available magnesium prepara 2008 Apr. 15: 105:5768-73). Magnesium is also important for tions have a magnesium absorption rates-40%. For example, brain function. For example, magnesium deficit is implicated magnesium oxide, which is perhaps the most widely used in attention deficit hyperactivity disorder (Kozielec T. Staro magnesium Supplement, has a magnesium absorption rate of brat-Hermelin B. Magnes Res. 1997 June; 10:143-8; Mou only about 4% (Firoz M, Graber M. Bioavailability of US sain-Bosc M. Roche M. Polge A, Pradal-Prat D. Rapin J. Bali commercial magnesium preparations. Magnes Res. 2001 J. P. Magnes Res. 2006 March; 19:46-52), affective disorders December; 14:257-62)). The present invention provides con (Murck H. Nutritional neuroscience. 2002 December; 5:375 trolled release magnesium compositions for use as a magne 89), Alzheimer's disease (Andrasi E. Pali N. Molnar Z, Kosel sium dietary Supplement. S. J Alzheimers Dis. 2005 August: 7:273-84: Cilliler A E, Ozturk S, Ozbakir S. Gerontology. 2007 Nov. 8:53:419-22: SUMMARY OF THE INVENTION Lemke M R. Biol Psychiatry. 1995 Mar. 1; 37:341-3), 0006 To supply the population with sufficient magne migraine (Ramadan N M. Halvorson H. Vande-Linde A, sium, a very high dose of magnesium Supplement is required Levine S R, Helpern JA, Welch K M. Headache. 1989 Octo to reach the recommended daily allowance (RDA). For ber; 29:590-3; Facchinetti F, Sances G, Borella P. Genazzani example, 4 grams of magnesium oxide would be required as A R, Nappi G. Magnesium prophylaxis of menstrual an oral Supplement. A slow release magnesium composition migraine: effects on intracellular magnesium. Headache. offers several advantages. Slow release avoids high concen 1991 May: 31:298-301), and Autism (Martineau J, Bar tration of magnesium in the gastrointestinal (GI) tract. Unab thelemy C, Garreau B. Lelord G. Biol Psychiatry. 1985 May; sorbed magnesium in the GI tract often leads to diarrhea. 20:467-78; Pfeiffer SI, Norton J, Nelson L, Shott S. JAutism Slow release can avoid accumulation of unabsorbed magne Dev Disord. 1995 October; 25:481-93; Strambi M, Longini sium and reduce Such adverse effects. The present invention M. Hayek J. Berni S, Macucci F. Scalacci E, VeZZosi P. Biol discloses such dosage forms and methods of use thereof. Trace Elem Res. 2006 February: 109:97-104). 0007. In one aspect, the present invention provides an oral 0004 Recently, it has been found that elevation of extra dosage form comprising magnesium (Mg) and threonate (T), cellular magnesium leads to a significant enhancement of wherein said threonate comprises one or more of a threonate synaptic plasticity and synaptic density in cultured hippoc salt or a threonate precursor, wherein said oral dosage form ampal neurons (Slutsky I, Sadeghpour S. Li B, Liu G. Neuron. has an in vitro dissolution profile in a dissolution medium, 2004 Dec. 2:44:835-49). The synaptic network is believed to and wherein said dissolution profile ranges between less than be involved in organization of neural circuits during early or equal to 5% in about 2 hours, less than 10% in about 4 development and in learning and memory processes. Indeed, hours, less than 40% in about 6 hours, greater than or equal to in patients with Alzheimer's disease, there is a strong inverse 60% in about 10 hours, and greater than or equal to 80% in correlation between the number of synapses and the degree of about 12 hours as measured using a USP type II (paddle) cognitive impairment (Terry R D, Masliah E. Salmon D. P. dissolution system at 75 rpm, at a temperature of 37° C. Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. Ann 0008. In some embodiments, the magnesium and thre Neurol. 1991 October 30:572-80: Selkoe DJ. Science. 2002 onate in said oral dose form is encapsulated in a tablet. In US 2015/0064285 A1 Mar.
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  • PHOTOPERIODISM the Value of Supplementary Illumination and Reduction of Light on Flowering Plants in the Greenhouse

    PHOTOPERIODISM the Value of Supplementary Illumination and Reduction of Light on Flowering Plants in the Greenhouse

    BULLETIN 512 OCTOBER, 1932 PHOTOPERIODISM The Value of Supplementary Illumination and Reduction of Light on Flowering Plants in the Greenhouse Alex Laurie and G. H. Poesch ... OHIO AGRICULTURAL EXPERIMENT STATION • Wooster, Ohio .. This page intentionally blank. II CONTENTS Introduction • . • . 3 Tests During 1.930-1931 . .. 3 The Effect of Increasing Length of Day by the Use of Additional Light 3 Pot Plants . 4 Bulbs; Roots, Corms, and Rhizomes ........................... 6 Bench Crops ................................................• 7 Annuals ................................................... 8 Herbaceous Perennials ....................................... 9 Temperatures . ........................... 11 Tests During the Season of 1931-1932 .................................. 11 Annuals ..................................................... 11 Length of Illumination . 12 Increasing Light Intensity During Cloudy Weather . 15 Perennials . 16 Pot Plants ................................................... 16 The Effect of Reduced Light . 18 Tests in 1931 . 20 The Time of Application from Date of Planting . 21 White Shades versus Black Shades . 22 Fertilizer Applications in Conjunction with Reduced Daylight . 23 Time of Application of Shade ..................................... 26 Variety Test . 26 Classification of Long- and Short-day Plants Tested in Experiments . 31 Discussion . 32 Commercial Value . .. 33 Specific Recommendations . 34 Summary ........................................................... 35 Bibliography . 37 (1) • This page