WO2003033020A1

WO2003033020A1 - Composition and method to treat post-illness wasting phenomenon

Info

Publication number: WO2003033020A1
Application number: PCT/US2002/033061
Authority: WO
Inventors: Stephen E. Bachman; Michael E. Hubbert; Michael L. Galyean
Original assignee: Ganado Research, L.L.C.
Priority date: 2001-10-17
Filing date: 2002-10-17
Publication date: 2003-04-24

Abstract

A method to treat post-illness wasting phenomenon in animals. The method first forms an ingestible composition which includes Glutamine, Taurine, Vitamin E, Vitamin C, and Zinc. That ingestible composition is administered orally to the animal daily. In certain embodiments, the ingestible composition further includes Brewers Yeast. In certain embodiments, the ingestible composition further includes whey protein. In certain embodiments, the composition further includes an amino acid component comprising Alanine, Aspartic acid, Glutamic acid, Isoleucine, Leucine, Lysine, Phenylalanine, Serine, Threonine, Tryptophan, and Valine. In certain embodiments, the amino acid component further includes Arginine, Cystine/Cystine, Glycine, Histidine, Methionine, Proline, and Tyrosine.

Description

COMPOSITION AND METHOD TO TREAT POST-ILLNESS WASTING

PHENOMENON Field Of The Invention

The invention relates to an ingestible composition for oral administration to animals, including humans. In certain embodiments, the ingestible composition comprises a liquid drink, drench or paste. The invention further relates to a method using Applicants' composition to treat post-illness wasting phenomenon.

Background Of The Invention After receiving treatment for one or more illnesses, certain animals experience a "wasting phenomenon" that is characterized by a variety of maladies, including increased incidence of infection and cancer, failure to grow, allergies, and/or neuromuscular ailments. During this period the animal's immunological defenses are diminished and weight loss becomes "chronic." In production animals incidences of such a "wasting phenomenon" can result in economic loss, because these animals are usually sold at a lighter weight and have converted feed less efficiently. In companion (non-production) animals or humans this condition can retard or negate recovery to a healthy state.

What is needed is an effective, easily administered treatment for such animals that can effectively restore the animal's appetite. Such increased appetite leads to increased food consumption, which generally, results in weight gain and a return to more normal health. Applicants' invention comprises such an effective, easily administered, appetite-restoring, composition and method.

Summary Of The Invention Applicants' invention includes a method to treat post-illness wasting phenomenon in animals, including humans. Applicants' invention further includes a method to maintain the health of animals, including humans. Applicants' methods first form an ingestible composition which includes Glutamine, Taurine, Vitamin E, Vitamin C, and Zinc. That ingestible composition is daily administered orally to the animal. In certain embodiments, Applicants' ingestible composition further includes Brewers Yeast. In certain embodiments, Applicants' ingestible composition further includes whey protein. In certain embodiments, Applicants' composition further includes an amino acid component comprising Alanine, Aspartic acid, Glutamic acid, Isoleucine, Leucine, Lysine, Phenylalanine, Serine, Threonine, Tryptophan, and Valine. In certain embodiments, the amino acid component further includes Arginine, Cystine / Cystine, Glycine, Histidine, Methionine, Proline, and Tyrosine.

Bibliography

1. Chirase, N. K., D. P. Hutcheson, and G. B. Thompson. 1991. Feed intake, rectal temperature, and serum mineral concentrations of feedlot cattle fed zinc oxide or zinc methionine and challenged with infectious bovine rhinotracheitis virus. J. Anim. Sci. 69:4137-4145.

2. Coelho, M. B. 1996. Influence of vitamin E on the performance and immune competence of feedlot cattle. In: M. B. Coelho (Ed.). Vitamin E in Animal Nutrition and Management (2^nd Ed.): A BASF Reference Manual, pp 317-331. BASF Corp., Mount Olive, NJ. 3. Franconi F, Bennardini F, Mattana A, et al. Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Am J Clin Nutr 1995;61:1115-1119.

4. Galyean, M. L., G. C. Duff, K. J. Malcolm, and D. R. Garcia. 1991. Effects of Pasteurella haemolytica vaccine and injectable vitamin E on the performance and health of newly received calves. Clayton Livestock Res. Ctr. Prog. Rep. No. 70, New Mexico Agric. Exp. Sta., Las Cruces.

5. Galyean, M. L., K. J. Malcolm-Callis, S. A Gunter, and R. A. Berrie. 1995. Effect of zinc source and level and added copper lysine in the receiving diet on performance by growing and finishing steers. Prof. Anim. Sci. 11:139-148. 6. Gardner, B. A., H. G. Dolezal, L. K. Bryant, F. N. Owens, and R. A.

Smith. 1999. Health of finishing steers: Effects on performance, carcass traits, and meat tenderness. J. Anim. Sci. 77:3168-3175.

7. Geggel HS, Ament ME, Heckenlively JR, et al. Nutritional requirement for taurine in patients receiving long-term parenteral nutrition. N Engl J Med 1985;312:142-146.

8. Johnson, R. W. 1997. Inhibition of growth by pro-inflammatory cytokines: An integrated view. J. Anim. Sci. 75:1244-1255. 9. Klasing, K. C. 1988. Nutritional aspects of leukocytic cytokines. J. Nutr. 118:1436-1446.

10. Lecker, S. H, V. Solomon, W. E. Mitch, and A. L. Goldberg. 1999. Muscle protein breakdown and the critical role of the Ubiquitin-Proteasome pathway in normal and disease states. J. Nutr. 129:227S-237S.

11. Lobley, G. E. S. O. Hoskin, and C. J. McNeil. 2001. Glutamine in animal science and production. J. Nutr. 131 :2525S-2531 S.

12. Newsholme, P. 2001. Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J. Nutr. 131:2515S-2522S.

13. Raiha N, Rassin D, Heinonen K, Gaull GE. Milk protein quality and quantity: Biochemical and growth effects in low birth weight infants (LBWI). Pediatr Res 1975;9:370.

14. Secrist, D. S., F. N. Owens, and D. R. Gill. 1997. Effects of vitamin E on performance of feedlot cattle: A review. Prof. Anim. Sci. 13:47-54.

15. Yamauchi, K., A. A. Adjei, C. K. Ameho, Y. Chan, A. D. Kulkarni, S. Sato, K. Okamoto, and S. Yamamoto. 1996. Nucleoside-nucleotide mixture and its components increase lymphoproliferative and delayed hypersensitivity responses in mice. J. Nutr. 126:1571-1577.

Detailed Description Of The Preferred Embodiments

Applicants' invention includes a composition and method to treat post-illness wasting phenomenon in animals, including humans. Applicants' invention further includes a composition and method to maintain the health of animals, including humans. In this embodiment of Applicants' method, Applicants' composition is prophylatically administered to animals, particularly to companion animals, to maintain an optimal level of health and well being. One such embodiment, for example, includes one or more gastrointestinal tract lubricants to facilitate expulsion of hair balls from feline companion animals. Certain embodiments of Applicants' composition include daily required levels of vitamins and minerals, plus additional levels of zinc, vitamin E, whey, one or more nucleotides, one or more nucleosides, glutamine, taurine/taurine derivatives, and combinations thereof. Alternative embodiments further include one or more flavorings at an aggregate amount of up to about ten weight percent, one or more fragrances at an aggregate amount of up to about one weight percent, one or more antibiotics at an aggregate amount of up to about fifty weight percent, one or more probiotics at an aggregate amount of up to about fifty weight percent, one or more additional vitamins at an aggregate amount of up to about twenty weight percent, one or more minerals at an aggregate amount of up to about twenty weight percent, one or more elements at an aggregate amount of up to about twenty weight percent, and combinations thereof.

Further in accordance with the present invention, Applicants' composition is suitable for oral administration to animals, including humans. In certain embodiments, Applicants' formulation is provided in a pharmaceutically acceptable carrier with or without an inert diluent. The carrier should be assimilable and edible and includes liquid, semi-solid, e.g. pastes, or solid carriers. Insofar as any conventional media, agent, diluent or carrier is not detrimental to the recipient animal, or to the therapeutic effectiveness of Applicants' formulation contained therein, its use in an orally administrable form for use in practicing the methods of the present invention is appropriate. Examples of carriers or diluents include sugars, fats, oils, water, glycerin, saline solutions, lipids, liposomes, thickening agents, resins, binders, fillers and the like, or combinations thereof. Zinc

In model systems in which cattle have been intentionally infected with respiratory viruses (Chirase et al., 1991), results with Zn have generally been positive, particularly with respect to positive effects of supplemental Zn on feed intake. Field studies have indicated some benefit of added Zn in receiving diets on decreasing morbidity from bovine respiratory disease (BRD; Galyean et al., 1995).

By "zinc," Applicants mean any compound that comprises zinc, for example zinc chloride, zinc acetate, zinc sulfate, and the like. "Zinc" further includes polymeric compositions capable of yielding free zinc ion but which contain zinc in another form. In certain polymeric release embodiments, Applicants' composition contains substantially chelated zinc ion. Applicants' composition includes zinc in an amount up to about two weight percent (2 wt %).

Vitamin E Vitamin E is known to have effects on the immune system (Coelho, 1996). Because of possible injection-site reactions, injections of vitamin E with some commercial preparations might be less desirable than dietary supplements or drenches (Galyean et al., 1991). Supplemental vitamin E in receiving diets seems to be beneficial for decreasing morbidity and improving performance. Secrist et al. (1997) pooled the results of five studies in which supplemental vitamin E was evaluated at levels of 450 to 1,600 IU/animal daily. Weighted means for daily gain tended (P < 0J4) to be increased (2.03 vs 1.76 lb/d), with no change in DMI, resulting in improved feed: gain (9 vs 12.4) with supplemental vitamin E. Morbidity tended to be less (P < 0J4) with vitamin E (48 vs 55%). These five trials included steers and steers plus bulls, with initial BW ranging from 534 to 600 lb. Percentage of concentrate in diets ranged from 10 to 74. Applicants' composition includes Vitamin E in an amount up to about five weight percent (5 wt %).

Whey The prime difference between whey (serum lactis) and whole milk is the near absence in the former of the caseins, the casein-bound calcium and phosphate, most of the fat and the fat soluble vitamins. The actual concentration in whey of "whey proteins" is usually similar to that in milk. The caseins represent about eighty weight percent (80 wt %) of the total protein content of cows milk while whey proteins comprise about twenty weight percent (20 wt %). The separation of the whey protein component from the caseins renders the amino acid profile and associated small peptides patterns of whey proteins unaltered by that of the caseins, once the digestive process has released free amino acids from all ingested proteins. Both specific and non-specific immune responses affect metabolism in a variety of ways, including decreased feed intake, increased energy expenditure, oxidization of glucose, decreased fatty acid uptake by adipocytes, and changes in the distribution of Zn and other trace minerals in the body (Klasing, 1988). These effects are related to the production of cytokines by leukocytes. Although a wide variety of cytokines are produced by the leukocytes in response to infectious and inflammatory agents, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor α ("TNFα") seem to be responsible for the effects on intermediary metabolism (Klasing, 1988). These pro-inflammatory cytokines ("PIC") might be involved in the negative effects of BRD on growth rate and carcass characteristics of beef cattle. Johnson (1997) concluded that these compounds have profound effects on behavioral and neuroendocrine systems as well as intermediary metabolism. Pro- inflammatory cytokines increase muscle protein breakdown, increase lipolysis, stimulate oxidation of glucose and gluconeogenesis, and decrease serum Fe and Zn concentrations (Klasing, 1988; Johnson, 1997). The PIC can act both centrally, through receptors in the brain, and peripherally, potentially inhibiting growth both directly and indirectly (Johnson, 1997). A wasting syndrome in pigs has been linked to the PIC, and these compounds have been suggested as being responsible for decreased lean growth by pigs reared under immunologically challenging conditions (Johnson, 1997). The role of PIC in beef cattle that succumb to BRD is unknown; however, the lower BW gain, lower carcass weight, and decreased USDA quality grade in cattle treated for BRD and(or) displaying pneumonic lung lesions at slaughter (Gardner et al., 1999) might reflect the potent effects of the PIC or related hormones and metabolites on protein and lipid metabolism in these cattle. The Ubiquitin Proteasome (UP) pathway is the primary method by which intracellular protein occurs in body cells (Lecker et al., 1999). The pathway is activated by cytokines and glucocorticoids, which might account for the lower performance of cattle treated for BRD and for the occasional wasting conditions that can occur in such cattle. Insulin inhibits the UP pathway, thereby potentially counteracting the negative effects of cytokines and glucocorticoids.

Applicants' composition and method provide a source of carbohydrate and protein in the form of whey protein in Applicants' ingestible composition to stimulate insulin release and to decrease the negative effects of cytokines and glucocorticoids.

Applicants' composition includes whey protein in an amount up to about sixty weight percent (60 wt %).

Brewer's Yeast Saccharomyces cerevisiae, better known as Brewers Yeast, is a source of all the major B vitamins (except B12). It also contains other vitamins, sixteen amino acids and fourteen or more minerals.

Because Brewer's Yeast provides many B vitamins, it enhances the roles these vitamins play in the body. The B-complex vitamins assist in the metabolism of carbohydrates, fats, and proteins. In addition, different B vitamins play different roles, particularly in their support of the nervous system. When under the pressures of stress or infection, the body needs greater supplies of B vitamins. The body does not store excess B vitamins, so they must be regularly consumed. B vitamins can also help relieve morning sickness. Brewer's yeast is also a source of chromium. The U.S. FDA recommends 120 meg of chromium daily, but 90% of Americans are deficient in this important mineral.

Chromium has the ability to significantly lower blood cholesterol levels. In addition, chromium is also an important supplement for those with Type II (adult onset) diabetes because it can significantly lower blood sugar levels. Without chromium, insulin is not able to work properly and blood sugar levels rise. Researchers have been able to lower some diabetic glucose levels to almost normal levels with daily chromium doses of 1,000 meg.

In addition, Applicants have found that Brewer's Yeast supplies nucleic acid moieties. Nucleotides and nucleosides in the diet seem to be important in maintenance and stimulation of cellular immunity in nonruminant species (Yamauchi et al., 1996). In ruminants, levels of nucleotides and nucleosides provided to the small intestine would typically be high because of production of microbial cells in the rumen. Cattle that succumb to BRD would have low feed intakes, potentially resulting in lower quantities of nucleotides and nucleosides being absorbed from the small intestine, thereby exacerbating the negative of low feed intake on the cellular immune system. Applicants' composition includes Brewer's Yeast in an amount up to about fifteen weight percent (15 wt %).

Glutamine Glutamine is currently being considered as a conditionally essential amino acid during inflammatory conditions like infection and injury of animals (Newsholme, 2001) because it seems to be required for proliferation and function of immune system cells. In addition, supplemental glutamine has been beneficial for digestive tract health in young ruminants challenged by infection (Lobley et al., 2001). Muscle protein breakdown seems to be the major source of glutamine in animals under catabolic stress (Newsholme, 2001).

With a disease challenge and low feed intake, catabolic stress and muscle protein breakdown would be an expected condition in calves that succumb to BRD. Applicants' composition and method provides glutamine in an oral paste for morbid cattle to stimulate the immune system and maintain digestive tract health. Use of Applicants' composition and method is thought to decrease protein degradation and stimulate feed intake, leading to more rapid recovery from BRD. Applicants' composition includes glutamine in an amount up to about fifteen weight percent (15 wt %).

Taurine Taurine is a conditionally essential amino acid (essential in felines) that is not utilized in protein synthesis, but rather is found free or in simple peptides. Taurine has been shown to be essential in certain aspects of mammalian development, and in vitro studies in various species have demonstrated that low levels of taurine are associated with various pathological lesions, including cardiomyopathy, retinal degeneration, and growth retardation, especially if deficiency occurs during development. Metabolic actions of taurine include: bile acid conjugation, detoxification, membrane stabilization, osmoregulation, and modulation of cellular calcium levels. Clinically, taurine has been used with varying degrees of success in the treatment of a wide variety of conditions, including: cardiovascular diseases, hypercholesterolemia, epilepsy and other seizure disorders, macular degeneration, Alzheimer's disease, hepatic disorders, alcoholism, and cystic fibrosis. (Alt Med Rev 1998;3(2):128-136)

Taurine was first discovered as a component of ox bile in 1827, it was not until 1975 that the significance of taurine in human nutrition was identified, when it was discovered that formula-fed, pre-term infants were not able to sustain normal plasma or urinary taurine levels. Signs of taurine deficiency have also been detected in children on long-term, total parenteral nutrition, and in patients with "blind-loop" syndrome. In vivo studies in various species have shown taurine to be essential in certain aspects of mammalian development, and have demonstrated that low levels of taurine are associated with various pathological lesions, including cardiomyopathy, retinal degeneration, and growth retardation, especially if deficiency occurs during development.

Derived from methionine and cysteine metabolism, taurine is known to play an important role in numerous physiological functions. While conjugation of bile acids is perhaps its best-known function, this accounts for only a small proportion of the total body pool of taurine in humans. Other metabolic actions of taurine include: detoxification, membrane stabilization, osmoregulation, and modulation of cellular calcium levels. Both plasma and platelet taurine levels have been found to be depressed in insulin-dependent diabetic patients; however, these levels were raised to normal with oral taurine supplementation. In addition, the amount of arachidonic acid needed to induce platelet aggregation was lower in these patients than in healthy subjects. Taurine supplementation reversed this effect as well, reducing platelet aggregation. In vitro experiments demonstrated that taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, while having no effect on the aggregation of platelets from healthy subjects. Applicants' composition includes taurine in an amount up to about six weight percent (6 wt %).

The following examples are presented to further illustrate to persons skilled in the art how to make and use Applicants' invention and to identify presently preferred embodiments thereof. These examples are not intended as a limitation, however, upon the scope of Applicants' invention, which is defined only by the appended claims.

EXAMPLE I Table 1 summarizes the ingredients comprising one embodiment of Applicants' composition. The formulation of Example I was incorporated into an oral gel. The dosage used for the formulation of Example I is between about 1 to about 10 g of formulation per kilogram of body weight. In alternative embodiments, Applicants' method utilizes less than 1 gram of formulation per kilogram of animal body weight. In still other embodiments, Applicants' method includes using more than about 10 grams of formulation per kilogram of body weight.

TABLE 1

EXAMPLE π

Alternative embodiments of Applicants' composition include a mixture of amino acids rather than Whey protein. In combination with Glutamine and Taurine, these embodiments of Applicants' composition have the amino acid component recited in Table 2. The percentages of Table 2 comprise weight percentages of the amino acid component. In these embodiments, Applicants' composition includes the amino acid component of Table 2 in an amount up to about sixty weight percent (60 wt %). TABLE 2

In certain embodiments, Applicants' amino acid component includes Alanine, Aspartic acid, Glutamic acid, Isoleucine, Leucine, Lysine, Phenylalanine, Serine, Threonine, Tryptophan, and Valine. In certain embodiments, Applicants' amino acid component further includes Arginine. In certain embodiments, Applicants' amino acid component further includes Cystine / Cysteine. In certain embodiments, Applicants' amino acid component further includes Glycine. In certain embodiments, Applicants' amino acid component further includes Histidine. In certain embodiments, Applicants' amino acid component further includes Methionine. In certain embodiments, Applicants' amino acid component further includes Proline. In certain embodiments, Applicants' amino acid component further includes Tyrosine. Applicants' composition can be formed with or without binders, carriers, surfactants, buffering agents, fragrances, flavorings, dispersing agents, and the like. During the mixing operation, the various components can be added in any order. Conventional mixing techniques can be used to blend the various ingredients. In certain high percentage solids embodiments, the components are dry blended, extruded, and then formed into pellets or flakes. In these embodiments, the components of Table 1, for example, comprise ninety weight percent or more of the final composition.

In certain medium percentage solids embodiments, the composition includes one or more carrier components, such as water, fats, oils, glycerin, lipids, liposomes, thickening agents, and the like. In these embodiments, the components of Table 1, for example, comprise between about fifty weight percent and about ninety weight percent of the final composition. In certain of these embodiments, the composition comprises a paste having a bulk viscosity of about 100,000 centipoises or more. In certain low percentage solids embodiments, the components of Table 1, for example, comprise less than about fifty weight percent of the final composition. In certain of these embodiments, the composition comprises a paste having a bulk viscosity of less than about 100,000 centipoises.

Applicants' invention includes a method to maintain a healthy animal's appetite and well being. In these embodiments, Applicants' method includes feeding a healthy animal pellets or flakes formed using Applicants' composition. Applicants have found it useful to include daily such pellets / flasks in an amount up to about twenty-five percent of the animal's normal daily food intake.

As the health of an animal deteriorates, the animal's food intake decreases. Applicants have found it efficacious to administer Applicants' composition in the form of a paste to animals recovering from, for example, an illness or surgery. As those skilled in the art will appreciate, the viscosity of the paste can be adjusted, along with inclusion of various flavorings, to enhance the efficacy of administration.

While the preferred embodiments of the present invention have been illustrated in detail, it should be apparent that modifications and adaptations to those embodiments may occur to one skilled in the art without departing from the scope of the present invention as set forth in the following claims.

Claims

We claim:

1. An ingestible composition for animals, including humans, comprising: Glutamine;

Taurine; Vitamin E;

Vitamin C; and Zinc.

2. The composition of claim 1, further comprising one or more gastrointestinal tract lubricants.

3. The compositions of claims 1 or 2, further comprising Brewers Yeast.

4. The composition of claims 1, 2, or 3, further comprising whey protein.

5. The composition of claims 1, 2, or 3, further comprising an amino acid component which includes:

Alanine; Aspartic acid;

Glutamic acid;

Isoleucine;

Leucine;

Lysine; Phenylalanine;

Serine;

Threonine;

Tryptophan;

Valine.

6. The composition of claim 5, wherein said amino acid component further comprises:

Arginine;

Cystine / Cysteine;

Glycine; Histidine;

Methionine;

Proline; and Tyrosine.

7. The composition of claim 6, wherein said amino acid component comprises:

Alanine between about 3 weight percent and about 6 weight percent; Arginine up to about 3 weight percent;

Aspartic acid between about 7 weight percent and about 12 weight percent;

Cystine / Cysteine up to about 3 weight percent;

Glutamic acid between about 16 weight percent and about 25 weight percent;

Glycine up to about 3 weight percent; Histidine up to about 3 weight percent;

Isoleucine between about 3 weight percent and about 6 weight percent;

Leucine between about 7 weight percent and about 11 weight percent;

Lysine between about 6 weight percent and about 9 weight percent;

Methionine up to about 6 weight percent; Proline up to about 43 weight percent;

Phenylalanine between about 4 weight percent and about 7 weight percent;

Serine between about 3 weight percent and about 6 weight percent;

Threonine between about 4 weight percent and about 8 weight percent;

Tryptophan between about 0.4 weight percent and about 2 weight percent; Tyrosine up to about 4 weight percent; and

Valine between about 3 weight percent and about 6 weight percent.

8. The composition of claim 6, wherein said composition comprises at least ninety weight percent solids, and wherein said composition is formed into pellets.

9. The composition of claim 6, wherein said composition comprises at least ninety weight percent solids, and wherein said composition is formed into flakes.

10. The composition of claim 6, further comprising a carrier, wherein said carrier is selected from the group consisting of water, fats, oils, glycerin, lipids, liposomes, thicking agents, and combinations thereof.

11. The composition of claim 10, wherein said composition comprises between about fifty weight percent solids and about ninety weight percent solids.

12. The composition of claim 10, wherein said composition comprises less than about fifty weight percent solids.

13. A method to treat post-illness wasting phenomenon in animals, comprising the steps of: forming an ingestible paste comprising Glutamine, Taurine, Nitamin E,

Vitamin C, and Zinc; administering orally said paste to said animal daily.

14. The method of claim 13, wherein said paste further comprises Brewers Yeast.

15. The method of claims 13 or 14, wherein said paste further comprises whey protein.

16. The method of claims 13 or 14, wherein said paste further comprises an amino acid component which includes:

Alanine; Aspartic acid;

Glutamic acid;

Isoleucine;

Leucine;

Lysine; Phenylalanine;

Serine;

Threonine;

Tryptophan;

Valine.

17. The method of claim 16, further comprising the steps of: extruding said composition; forming flakes from said extruded composition.

18. The method of claim 16, further comprising the steps of: extruding said composition; and forming pellets from said extruded composition.

19. The method of claim 16, further comprising the steps of: mixing one or more carriers with said composition; forming a paste from said mixture.

20. The method of claim 19, wherein said one or more carriers are selected from the group consisting of water, fats, oils, glycerin, lipids, liposomes, thickening agents, and combinations thereof.