Patent Application
20070254026
The following examples are provided for the purpose of illustration of the invention and not limitation of the invention. A skilled person may use these for guidance in creating the desired softgel capsule formulation, in accordance with the present invention:
A number of considerations need to be taken into account when manufacturing capsules. One is capsule size. The upper size limit which most consumers find acceptable is about 1.20 g, a size commonly used for fish oil supplements. The second consideration is the number of capsules needed to be taken per day. As a matter of practicality, the upper limit is 4 to 6 capsules per day. At the larger capsule size, an oblong shape (1000 mg or more) is preferred as this is easier to swallow. Of course, the present invention is not limited by these parameters.
Phytosterols: The number of portions per day of phytosterol containing products is regulated in the United States and in the European Union. The FDA health claim for phytosterols, requires two servings per day (FDA#1). The European Union requires that phytosterols be dosed in either one portion per day or three portions per day but not two portions (EU labelling regulation). Another consideration is the minimum dose needed for efficacy. The FDA has set this dose at 0.8 g/day. The European Union has not set a minimum dose, but has set a maximum allowable dose of 3.0 g/day. Studies done with the applicant's proprietary tall oil sterols show that a near maximal lowering of LDL occurs at a dose of 1.8 g/day when taken with meals three times a day. The preferred dosage for lowering LDL cholesterol is 1.8 g per day in divided doses.
Omega-3-fatty acids: The FDA recommends that supplement products be labelled to deliver less than 1 g/day (FDA #2). The FDA recommends an upper limit of 3 g/day for intake from supplement products and foods. The American Heart Association recommends a daily intake of 500-1800 mg/day of omega-3-fatty acids from supplements and fish sources.
In the following examples, the capsule fill volumes have been kept below 1200 mg by increasing the number of capsules required per day to provide the indicated dosage. The content of sterol esters have been kept above 20% of the fill weight and the content of free sterols/stanols has been kept below 40% to avoid the problem of re-crystallization of the sterols/stanols below the capsule shell. Exceptions are examples 34 and 35 where the sterol content is low enough to dissolve in the lipid fraction. In some of the examples, where there is a high proportion of the fill as omega-3-fatty acids it may be necessary to add a thickening agent to maintain the free sterols/stanols in suspension during the capsule filling operation. With higher proportions of sterol esters, this is unnecessary.
The relative proportions of sterols and omegas depends on the market. If the consumer views the omega-3-fatty acid content as the more important parameter, formulations as shown in Tables 2, 3 and 9 might be preferred. The cholesterol reduction claim for sterols is much stronger in the United States; it is a full claim. The omega fatty acid health claim is only a qualified claim and must include the statement “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3-fatty acids may reduce the risk of heart disease”. If the phytosterol component is to be emphasized, there are many formulations clearly showing this preference. If the objective is maximum efficacy of both components, other formulations clearly show this.
The fish source omega-fatty acids have two active components, DHA and EPA. These have different activities. For example, DHA is effective in preventing certain brain disorders. Fish oil omega fatty acids are available with different ratios of DHA and EPA, these generally have a purity of about 60%. The type of oil used can be varied depending on the purpose of the supplement. Such is within the purview of a skilled person in this field.
Formulations 1-7 would be useful to reduce the risk of cancer, Alzheimer's disease or other neurodegenerative diseases. The preferred mixture would be formulation 5.
Formulations 8 and 9 are intended for use in ameliorating the symptoms of benign prostate hypertrophy. The effective doses of sitosterol (tall oil sterols) are 20 to 60 mg per day.
Formulations 10-16 are essentially the same as formulations 3 and 4 except that the stanol content of the capsules has been increased from that typical of tall oil sterols (11.6%) to 16%, 18%, and 20%. Increasing the tall stanol content slightly reduces the volume of the fill because the amount of ester required to fill out the total dose of phytosterols is reduced.
Some of the preferred formulations shown relate primarily to the prevention of cardiovascular disease. A cholesterol reduction claim is allowed in the United States. The EU labelling regulation allows use of the statement “this product is intended only for persons who want to lower their blood cholesterol”. In the some of the examples provided, dosages of 4 and 6 capsules per day are used. The health claim allows instructions based on two servings per day. The EU labelling regulation requires that dosing instructions be based on either one serving per day or three servings per day but not two. The 4 per day examples can be used in the United States. For example, take two capsules twice a day. The 6 capsules per day examples can be used in either area. For example, in the U.S., take 3 capsules twice a day. In the EU the instruction would be take 2 capsules three times per day.
Formulation number 10 was tested on commercial scale encapsulation equipment with very good results. On a 50 kg batch, capsule recoveries were 95%.
Capsule ingredients:
The fish oil was poured into a mixing vessel and stanols added. The stanols dissolved almost immediately in omega fatty acid oil. The indicated amount of sterol esters were warmed to point where the indicated amount of could be added to the mixing vessel. The mixture was then encapsuled with a beef gelatin (BSE free) containing glycerin, water, titanium dioxide masking agent and a light yellow colouring agent. The capsule shape used was oblong. The capsules were dried for two days at room temperature before packaging.
Capsules can be either animal based gelatin (beef, pork, or fish) or vegetable based gelatin. Colour and shape are optional. An off-odour sometimes comes from the animal gelatins or the fish oil. Vanillin has been found to be a good odour masking agent when incorporated into the gelatin.
Softgel capsule Filler Composition of:
0.344% stanol
11.5% sterol esters
| Number | Date | Country | |
|---|---|---|---|
| 60796990 | May 2006 | US |
