(12) Patent Application Publication (10) Pub. No.: US 2016/0081976 A1 Bromley (43) Pub
Total Page：16
File Type：pdf, Size：1020Kb
US 20160O81976A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0081976 A1 Bromley (43) Pub. Date: Mar. 24, 2016 (54) FORMULATIONS OF WATER-SOLUBLE A6II 45/06 (2006.01) DERVATIVES OF VITAMIN E AND SOFT A63L/22 (2006.01) GEL COMPOSITIONS, CONCENTRATES A61E36/324 (2006.01) AND POWDERS CONTAINING SAME A61E36/85 (2006.01) (71) Applicant: VIRUN, INC., Walnut, CA (US) A647/48 (2006.01) O O A613 L/437 (2006.01) (72) Inventor: Philip J. Bromley, Fullerton, CA (US) (52) U.S. Cl. (21) Appl. No.: 14/866,808 CPC ......... A61 K3I/355 (2013.01); A61K47/48215 (2013.01); A61 K3I/09 (2013.01); A61 K (22) Filed: Sep. 25, 2015 31/202 (2013.01); A61K 31/437 (2013.01); Related U.S. Application Data A6 IK3I/122 (2013.01); A61K 36/324 (2013.01); A61K 36/185 (2013.01); A61 K (63) Continuation of application No. PCT/US2015/ 45/06 (2013.01) 051097, filed on Sep. 18, 2015, Continuation of appli cation No. PCT/US2015/051083, filed on Sep. 18, 2015. (57) ABSTRACT (60) Provisional application No. 62/052,433, filed on Sep. RA's prcity, application N. R Provided herein are compositions that contain water-soluble ed. On Sep. 1S, prov1s1onal application No. itamin E derivati ixtu iti has toco 62/052,435, filed on Sep. 18, 2014, provisional appli- N 1 N. 1Ve t t E. aS f cation No. 62/052,450, filed on Sep. 18, 2014. pheryl polyethylene glycol Succinate ( ), analogS, TPGS homologs and TPGS derivatives. The water-soluble Publication Classification Vitamin E mixtures contain mixtures of dimers and mono (51) Int. Cl mers of the vitamin E derivative. Provided are products con A. 6iK I/355 (2006.01) taining the water-soluble vitamin E derivative mixtures, A6 IK3I/09 (2006.01) including capsules, soft gel compositions, pre-gel composi A6 IK3I/202 (2006.01) tions, emulsions and powders. US 2016/008 1976 A1 Mar. 24, 2016 FORMULATIONS OF WATER-SOLUBLE tion Ser. No. 61/852,243, filed Mar. 15, 2013, entitled “FOR DERVATIVES OF VITAMIN E AND SOFT MULATIONS OF PEG-DERIVATIVES OF VITAMIN E GEL COMPOSITIONS, CONCENTRATES AND COMPOSITIONS CONTAINING SAME, to Philip AND POWDERS CONTAINING SAME Bromley, and International PCT Application No. PCT/ US2014/25006, filed Mar. 12, 2014, published as WO 2014/ RELATED APPLICATIONS 151109 on Sep. 25, 2014, entitled “FORMULATIONS OF 0001. This application is a continuation of PCT/US2015/ WATER-SOLUBLE DERIVATIVES OF VITAMIN E AND 051097, filed Sep. 18, 2015, entitled “PRE-SPRAY EMUL COMPOSITIONS CONTAINING SAME, which also SIONS AND POWDERS CONTAINING NON-POLAR claims priority to U.S. Provisional Application Ser. No. COMPOUNDS.” to Philip Bromley, which claims the benefit 61/852,243, filed Mar. 15, 2013, entitled “FORMULATIONS of priority to U.S. Provisional Application Ser. No. 62/052, OF PEG-DERIVATIVES OF VITAMINE AND COMPOSI 433, filed Sep. 18, 2014, entitled “PRE-SPRAY EMUL TIONS CONTAINING SAME and to U.S. Provisional SIONS AND POWDERS CONTAINING NON-POLAR Application Ser. No. 61/863,732, filed Aug. 8, 2013, entitled COMPOUNDS,” to Philip J. Bromley, and to U.S. Provi FORMULATIONS OF WATER-SOLUBLE DERIVA sional Application Ser. No. 62/052,450, filed Sep. 18, 2014, TIVES OF VITAMIN E AND COMPOSITIONS CON entitled “FORMULATIONS OF WATER-SOLUBLE TAINING SAME, each to Philip Bromley. DERIVATIVES OF VITAMINE AND SOFT GEL COMPO 0006. The subject matter of each of the above-referenced SITIONS, CONCENTRATES AND POWDERS CON applications is incorporated by reference in its entirety. TAINING SAME, to Philip J. Bromley. 0002 This application also is a continuation of PCT/ FIELD OF THE INVENTION US2015/051083, filed Sep. 18, 2015, entitled “SOFT GEL 0007 Provided herein are compositions that contain COMPOSITIONS AND PRE-GEL CONCENTRATES to water-soluble vitamin E derivative mixtures (compositions), Philip J. Bromley, which also claims the benefit of priority to such as tocopheryl polyethylene glycol succinate (TPGS), U.S. Provisional Application Ser. No. 62/052,435, filed Sep. TPGS analogs, TPGS homologs and TPGS derivatives. The 18, 2014, entitled “SOFT GEL COMPOSITIONS AND water-soluble vitamin E mixtures contain mixtures of dimers PRE-GEL CONCENTRATES. to Philip J. Bromley, and to and monomers of the vitamin E derivative. Also provided are U.S. Provisional Application Ser. No. 62/052.450, filed Sep. products containing the water-soluble vitamin E derivative 18, 2014, entitled “FORMULATIONS OF WATER mixtures, including soft gel compositions, pre-gel concen SOLUBLE DERIVATIVES OF VITAMIN E AND SOFT trates, capsules and soft gels compositions that contain the GEL COMPOSITIONS, CONCENTRATES AND POW pre-gel concentrates, and powders, and methods for prepar DERS CONTAINING SAME to Philip J. Bromley. ing the products. Methods for preparing the products are 0003. This application is related to U.S. application Ser. provided. No. 14/866,717, filed the same day herewith, entitled “PRE SPRAY EMULSIONS AND POWDERS CONTAINING BACKGROUND NON-POLAR COMPOUNDS.” to Philip J. Bromley. U.S. application Ser. No. 14/866,717 also claims priority to U.S. 0008. Non-polar ingredients and compounds are not eas Provisional Application Ser. No. 62/052,433, filed Sep. 18, ily dissolved in aqueous solutions, such as water or other 2014, entitled “PRE-SPRAY EMULSIONS AND POW polar solvents. A number of non-polar ingredients and com DERS CONTAINING NON-POLAR COMPOUNDS to pounds are used in compositions for human ingestion. These Philip J. Bromley, and to U.S. Provisional Application Ser. include, for example, pharmaceuticals, nutraceuticals and/or No. 62/052,450, filed Sep. 18, 2014, entitled “FORMULA dietary Supplements. Exemplary of non-polar ingredients are TIONS OF WATER-SOLUBLE DERIVATIVES OF VITA Vitamins and minerals, fatty acids, and other non-polar com MIN E AND SOFT GEL COMPOSITIONS, CONCEN pounds, non-polar bioactive agents and non-polar ingredi TRATES AND POWDERS CONTAINING SAME to ents. Because of poor water Solubility, inclusion of non-polar Philip J. Bromley. ingredients and compounds in products for human consump 0004. This application also is related to U.S. application tion, for example, in Supplements, foods and beverages, can Ser. No. 14/866,724, filed the same day herewith, entitled be problematic, and the amount of non-polar ingredient that SOFT GEL COMPOSITIONS AND PRE-GEL CONCEN can be included is limited. TRATES.” to Philip J. Bromley. U.S. application Ser. No. 0009 Water-soluble forms of vitamin E, such as TPGS 14/866,724 also claims priority to U.S. Provisional Applica (D-O-tocopheryl polyethylene glycol Succinate), in particular tion Ser. No. 62/052,435, filed Sep. 18, 2014, entitled “SOFT TPGS 1000 (D-C-tocopheryl polyethylene glycol 1000 suc GEL COMPOSITIONS AND PRE-GEL CONCEN cinate), have been approved by the FDA as vitamin E nutri TRATES.” to Philip J. Bromley, and to U.S. Provisional tional supplements. TPGS is a stable, tasteless and odorless Application Ser. No. 62/052,450, filed Sep. 18, 2014, entitled source of readily bioavailable vitamin E that does not hydro FORMULATIONS OF WATER-SOLUBLE DERIVA lyze under normal conditions. TPGS, TPGS homologs, TPGS TIVES OF VITAMIN E AND SOFT GEL COMPOSI analogs and TPGS derivatives also are used as Surfactants, TIONS, CONCENTRATES AND POWDERS CONTAIN and have been used to prepare stabilized formulations of food, ING SAME, to Philip J. Bromley. beverage, pharmaceutical or nutraceutical products contain 0005. This application also is related to U.S. patent appli ing non-polar compounds. TPGS (and homologs, analogs and cation Ser. No. 14/207,310, filed Mar. 12, 2014, published as derivatives) has been used as a solubilizing agent for Such US-2014-0271593-A1 on Sep. 18, 2014, entitled “FORMU stabilized formulations, such as water-soluble formulations LATIONS OF WATER-SOLUBLE DERIVATIVES OF that contain water-insoluble non-polar compounds, such as VITAMIN E AND COMPOSITIONS CONTAINING drugs, vitamins, or other biologically active compounds, Such SAME.” which claims priority to U.S. Provisional Applica as natural and non-natural omega-fatty acids. Thus, TPGS US 2016/008 1976 A1 Mar. 24, 2016 possesses the dual function of providing additional dietary of the dimer form of the vitamin E derivative product. One Vitamin E and providing stabilization to a formulation. advantageous property of the higher dimer-containing water 0010 Available products containing non-polar com soluble vitamin E derivative compositions is that, when pounds, particularly products for human consumption, Such diluted into foods and beverages, the resulting products have as food and beverage products containing non-polar com greater clarity and stability than products produced by addi pounds, and methods for formulating Such products, are lim tion of the same concentrates, except that the concentrates ited. In addition, the amount, or concentration, of non-polar containa water-soluble vitamin Ederivative composition that compounds in available food and beverage products is limited contains less than 13% dimer. due to the display of undesirable organoleptic properties 0014 Generally, vitamin E derivative compositions have when the amount of non-polar compound is increased. Thus, been prepared to contain as much monomer form as possible there is a need to develop products for human consumption, and contain dimer only as an undesired byproduct in low Such as food and beverage products, that contain non-polar concentration. The water-soluble vitamin E derivative mix compounds and methods for making the products. There is an tures (compositions) provided herein can be used as the PEG additional need to develop products for human consumption, derivative of vitamin E, such as TPGS, in addition to or in Such as food and beverage products, that contain a higher place of another Surfactant, such as a polysorbate, in any amount of non-polar compound than is offered in available composition or formulation that contains a PEG derivative of food and beverage products.