Formulations and methods for delivering dietary and pharmaceutical ingredients

Abstract

The present invention relates to a base gel formulation into which nutritional or pharmaceutical ingredients can be incorporated. The base formulation is designed for people with dysphagia. The base formulation contains three different gelling agents, with the amounts of gelling agents varied to conform to the International Dysphagia Diet Standardization Initiative (IDDSI) 2019, which characterizes the formulated gel as a Type 1-4 product. The base formulation contains alginate as the primary gelling agent, cross-linked with divalent cations to provide structural integrity, and its gelling properties are further modified by the inclusion of low-methoxy pectin and agar, as secondary and tertiary gelling agents, respectively. While the gels contain significant amounts of water (hence Type 1-4 products are classified as beverages), Type 3 and 4 products may also be classified as foods. The gels also contain pH adjusters and preservatives, and may additionally contain flavorings.

Description

[Technical Field]

[0001] The present invention relates to formulations and methods for delivering dietary and medicinal ingredients to patients with swallowing difficulties or dysphagia. [Background technology]

[0002] Dysphagia patients have problems swallowing food and beverages. As a result, dietary and medicinal ingredients need to be delivered in forms that facilitate ingestion. While there are products on the market that are tailored to deliver specific ingredients to specific patient populations, patients and caregivers would benefit if there were "base formulations" that could facilitate the ingestion of a wide range of different dietary and medicinal ingredients in a format that conforms to the International Dysphagia Diet Standardization Initiative (IDDSI) 2019 edition. See https: / / iddsi.org / IDDSI / media / images / Complete_IDDSI_Framework_Final_31July2019.pdf, which is incorporated by reference and pages 2-10 are attached as Appendix 1.

[0003] The applicant previously disclosed in International Publication No. WO 2019215641 a gel formulation containing agar (the primary gelling agent) and alginate, which shears upon inhalation to release water and facilitate ingestion. However, agar can potentially form a "plug" and pose a choking hazard for patients with dysphagia. In contrast, the present invention uses alginate (along with selected divalent cations), which has a different gelling mechanism from agar, as the primary gelling agent to induce gelation and largely adhere to the IDDSI framework for producing gels with Type 1 to Type 4 textures. However, such gelling agents cannot achieve the required textures alone, and it was necessary to use other gelling agents (secondary and tertiary gelling agents) with different gelling mechanisms and select a given cationic compound to achieve the desired results.

[0004] Other technologies identified include: EP 3257528, which disclosed a drug-incorporated jelly for people with swallowing difficulties, used low methoxy (LM) pectin as the primary gelling agent, a significantly different approach and end product from the claimed invention.

[0005] JP 6265652 discloses a citrus inner peel-like food product containing agar and xanthan gum as primary gelling agents, but does not produce the soft gel of the claimed invention. JP 2018027901 A discloses a composition in which the primary gelling agent is a low methoxy pectin and the claimed texture of the present invention cannot be achieved.

[0006] Similarly, JP 200325041 A relies on low methoxy pectin, which fails to achieve the texture of the claimed invention. JP 2016202158 A discloses a jelly-containing beverage and uses LM pectin and alginate interchangeably, alone or together, to produce a gel.

[0007] None of this technology produces or leads one of ordinary skill in the art to the products claimed and detailed below. Summary of the Invention

[0008] According to the present invention, · With multiple gelling agents; · With water; pH adjusters and; Preservatives and; possibly Flavorings and A basic gel formulation conforming to the International Dysphagia Diet Standardization Initiative (IDDSI) 2019 edition, wherein the plurality of gelling agents comprises: · Agar and; · with alginate as the primary gelling agent; Low methoxy pectin and In accordance with the present invention, a base gel formulation is provided, characterized in that it comprises one of each of the following together with at least one divalent cation.

[0009] The basic formulation of the present invention is (1) A very thin, thick drink; (2) Thin, thick drinks; (3) Medium-thickness beverages; and (4) Thick, thick drinks, provides thickened products described as "beverages" under the IDDSI framework, including those defined as:

[0010] The present invention is based on combining three specific gelling agents with divalent ions to provide a stable base with a desired texture range. The three gelling agents are: (a) Agar - for strength and stability; (b) alginate - for flexibility; and (c) Low methoxy pectin - for smoothness, is.

[0011] The latter two gelling agents are (d) divalent cations - to cause gelation requires.

[0012] Applicants have surprisingly determined that it is essential that alginate be the primary gelling agent (present in the greatest amount) and that a divalent cation in the form of gluconate has advantages over the industry standard gelling agent, calcium chloride, which were not anticipated.

[0013] Other ingredients in the base gel drink include: (e) water; (f) pH adjusters; (g) preservatives; and optionally (h) Flavoring agent Examples include:

[0014] By careful control of the concentrations of each of the three gelling agents, the formulation can be modified to achieve a formulation that meets IDDSI viscosity criteria (1)-(4). As shown in Appendix 1, each of the types 1-4 products is classified as a beverage based on the defined syringe test method (although products 3 and 4 may also be considered a food).

[0015] The generic base formulation therefore includes a gelling agent and divalent cations in the weight percent amounts of the base formulation shown in Table 1a. The base formulation further includes non-gelling agent ingredients, including water.

[0016] [Table 1]

[0017] In one embodiment, the formulation does not contain flavorings as shown in Table 1b.

[0018] [Table 2]

[0019] In another embodiment, the formulation comprises a flavoring as shown in Table 1c.

[0020] [Table 3]

[0021] For example, natural flavorings such as orange juice may contain natural gelling agents which may affect the actual amounts of primary, secondary and tertiary gelling agents. Suitable general purpose base formulations are shown in Table 1d (with natural flavoring, eg, orange juice) and Table 1e (without flavoring).

[0022] [Table 4]

[0023] [Table 5]

[0024] Thus, formulations that comply with the IDDSI Thickness Criteria (1) include those shown in Table 2a (gelling agent in base formulation), Table 2b (containing natural flavoring, e.g., orange juice), and Table 2c (no flavoring).

[0025] [Table 6]

[0026] [Table 7]

[0027] [Table 8]

[0028] Thus, formulations that comply with the IDDSI Thickness Criteria (2) include those shown in Table 3a (gelling agent in base formulation), Table 3b (containing natural flavoring, e.g., orange juice), and Table 3c (no flavoring).

[0029] [Table 9]

[0030] [Table 10]

[0031] [Table 11]

[0032] Thus, formulations that comply with the IDDSI Thickness Criteria (3) include those shown in Table 4a (gelling agent in base formulation), Table 4b (containing natural flavoring, e.g., orange juice), and Table 4c (no flavoring).

[0033] [Table 12]

[0034] [Table 13]

[0035] [Table 14]

[0036] Thus, formulations that comply with the IDDSI thickness criteria (4) include those shown in Table 5a (gelling agent in base formulation), Table 5b (containing natural flavoring, e.g., orange juice), and Table 5c (no flavoring).

[0037] [Table 15]

[0038] [Table 16]

[0039] [Table 17]

[0040] The formulations of the present invention preferably contain calcium ions as the divalent cation. These are most preferably present in the form of calcium gluconate. All formulations of the present invention have a pH between pH 4 and pH 6, more preferably still between pH 5 and pH 6.

[0041] Preferred pH control agents are sodium hydroxide and citric acid. A preferred preservative is potassium sorbate. Optionally, the formulation includes a flavoring agent.

[0042] According to a second aspect of the present invention, there is provided a basic gel formulation which is a Type 1 to 3 formulation of an IDDSI according to the first aspect of the present invention packaged in a container which facilitates ingestion of the contents of the container by swallowing or sucking.

[0043] Preferably the container is a pouch, sachet or straw. According to a third aspect of the present invention there is provided a method of providing a patient with dietary and / or medicinal ingredients, the method comprising including the ingredients in an IDDSI Type 1-3 drinkable base gel formulation according to the first aspect of the present invention and allowing the patient to swallow or inhale the formulation.

[0044] In contrast to the second and third embodiments, IDDSI's Type 4 base gel formulation is still consumed without chewing, but is not free-flowing like a beverage. All four forms may be delivered in volumes between 5 mL and 200 mL depending on the meal and / or drug ingredients.

[0045] Examples demonstrating various aspects of the present invention are further described hereinafter with reference to the accompanying drawings. [Brief explanation of the drawings]

[0046] [Figure 1] Figure 1 shows the seven categories of artifacts included in the IDDSI framework. [Figure 2A] Figure 2A is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2B] Figure 2B is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2C] Figure 2C is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2D-1] Figure 2D is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2D-2] Figure 2D is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2E-1] Figure 2E is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2E-2] Figure 2E is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. [Figure 2E-3] Figure 2E is an excerpt from the referenced IDDSI document, providing details of syringe testing for types 1-4 products. DETAILED DESCRIPTION OF THE INVENTION

[0047] Referring to Figure 1, seven categories are classified as foods or beverages. The beverages become increasingly thick, starting from 0 (liquid) to 4 (thick beverages). Categories 3 (medium thickness beverages) and 4 (thick beverages) intersect with food categories 3, which are liquid foods, and 4, which are pureed foods.

[0048] In arriving at the base formulation(s) of the present invention, the Applicant carried out a great deal of experimentation with a view to finding gelling agents that complement each other, so that the gelling agents provided a flexible base that could be tailored to fit the different requirements of IDDSI "beverage" formulations, as subsequently defined by Categories 1 to 4.

[0049] Agar was initially considered an ideal candidate due to its ability to "release" water upon shear, but as shown in Comparative Example 1, agar alone proved inadequate. [Example]

[0050] Comparative Example 1 (agar)

[0051] [Table 18]

[0052] Multiple experiments carried out within the indicated ranges revealed that agar alone was too hard and would form large lumps when squeezed that would not crumble. Based on this, two other gelling agents were tested (as the sole agents) as shown in Comparative Examples 2 and 3.

[0053] Comparative Example 2 (Sodium alginate)

[0054] [Table 19]

[0055] The experiments carried out revealed that the sodium alginate gels were generally too thin and needed to be thickened. Comparative Example 3

[0056] [Table 20]

[0057] Experiments have shown that low-methoxy pectin produces thick, viscous gels, but they are not as stable as the other single-type gels. It became apparent from each of these standalone gelling agents that each had its own drawbacks, therefore applicants explored whether a combination could be utilized to address the drawbacks of each alone.

[0058] Therefore, in further development, three gelling agents were combined in different amounts (by weight) with a view to achieving a product that complies with the IDDSI guidelines. The methodology and suitable formulations are set out below.

[0059] Examples 4 to 7 General Methodology (including natural flavors, e.g., orange juice) Potassium sorbate, calcium gluconate, sodium hydroxide, flavoring, and water were weighed into a beaker and stirred until dissolved. The ingredients were heated until the solution reached a temperature of approximately 95°C. Once the temperature reached 95°C, the agar and LM pectin were added, and the blend continued to heat and stir until dissolved. Sodium alginate was slowly added and stirred until dissolved. The beaker was then removed from the heating plate and mixed in a high-shear laboratory mixer (Silverson® L5M) at 1500-2000 rpm for approximately 2 minutes to achieve a homogenous and smooth blend. The gel was then allowed to cool at room temperature. If the flavoring blend is not used, sodium hydroxide is replaced with citric acid.

[0060] Example 4a (IDDSI type 1) Utilizing the methodology previously described, a Type 1 formulation was prepared according to Table 10a below.

[0061] [Table 21]

[0062] IDDSI Type 1 is described as thicker than water and can flow through a straw and syringe. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, 1-4 mL should remain in the syringe after 10 seconds. The formulation of Example 4a left 2.6 mL remaining in the syringe.

[0063] Example 4b (IDDSI type 1) Utilizing the methodology previously described, a Type 1 formulation was prepared according to Table 10b below.

[0064] [Table 22]

[0065] IDDSI Type 1 is described as thicker than water and can flow through a straw and syringe. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, 1-4 mL should remain in the syringe after 10 seconds. The formulation of Example 4b left 2.5 mL remaining in the syringe.

[0066] Example 5a (IDDSI type 2) Utilizing the methodology previously described, a Type 2 formulation was prepared according to Table 11a below.

[0067] [Table 23]

[0068] IDDSI Type 2 is described as a liquid that can be poured down a spoon and slurped up, requiring only a small amount of force to swallow with a standard straw. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, 4-8 mL should remain in the syringe after 10 seconds. The formulation of Example 5a left 5.0 mL of liquid in the syringe.

[0069] Example 5b (IDDSI type 2) Utilizing the methodology previously described, a Type 2 formulation was prepared according to Table 11b below.

[0070] [Table 24]

[0071] IDDSI Type 2 is described as a liquid that can be poured down a spoon and slurped up, requiring only a small amount of force to swallow with a standard straw. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, 4-8 mL should remain in the syringe after 10 seconds. The formulation of Example 5b left 6.0 mL of liquid in the syringe.

[0072] Example 6a (IDDSI type 3) Utilizing the methodology previously described, Formulation Type 3 was prepared according to Table 12a below.

[0073] [Table 25]

[0074] IDDSI Type 3 describes a liquid that can be swallowed from a cup, eaten with a spoon, or swallowed directly without lumps. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, more than 8 mL must remain in the syringe after 10 seconds. The Example 6a formulation left 9.0 mL of liquid in the syringe.

[0075] Example 6b (IDDSI type 3) Utilizing the methodology previously described, Formulation Type 3 was prepared according to Table 12b below.

[0076] [Table 26]

[0077] IDDSI Type 3 is described as a liquid that can be swallowed from a cup, eaten with a spoon, or swallowed directly without lumps. The IDDSI flow test states that when the test liquid flows through a 10 mL slip-tip syringe, more than 8 mL must remain in the syringe after 10 seconds. The Example 6b formulation left 8.8 mL of liquid in the syringe.

[0078] Example 7a (IDDSI type 4) Utilizing the methodology previously described, Formulation Type 4 was prepared according to Table 13a below.

[0079] [Table 27]

[0080] Example 7b (IDDSI type 4) Utilizing the methodology previously described, Formulation Type 4 was prepared according to Table 13b below.

[0081] [Table 28]

[0082] IDDSI type 4 is described as a pureed food that can be eaten with a spoon, cannot be swallowed from a cup because it does not flow easily, cannot be sucked through a straw, and does not have lumps. The IDDSI flow test is not applicable to texture (4); the fork push test, fork drip test, and spoon tip test are applicable.

[0083] The fork push test states that the pureed food should be smooth, lump-free, and have very few particles. When a fork is pressed against the surface of the pureed food, the tines of the fork can make a clear impression on the surface, or the food retains grooves. The fork drip test states that the sample should pile up on the fork, and a small amount may run off the tines to form a short tail below, but should not drip continuously from the tines. The spoon tip test states that the product should be cohesive enough to hold its shape on a spoon, and when the spoon is turned sideways, a spoonful should drip off the spoon. All three test criteria are met for the formulations of Examples 7a and 7b.

[0084] Before arriving at a preferred formulation, Applicants noted that the selected cation, calcium chloride, often appeared to be "speckled" and contained "clumps," which were more evident in the "thicker" formulations. Applicants therefore tested calcium chloride to determine: a. magnesium chloride; and b. Calcium gluconate It was compared with other cations, including

[0085] The results of these tests (see Example 8 below) showed that calcium gluconate was very suitable for orange juice-based gels. Example 8

[0086] [Table 29]

[0087] The developed formulations containing calcium chloride produced undesirable spots and clumps. Calcium chloride is a common ingredient used to crosslink alginates. Due to its high solubility, it leads to rapid and uncontrolled gelation. The less water-soluble calcium salt, i.e., calcium gluconate, had significantly fewer spots and clumps than the other salts.

[0088] Magnesium ions formed very loose bonds and networks with alginate over a period of 2-3 hours, but magnesium chloride, while also producing fewer spots and clumps, proved impractical due to the looser gel formation.

Claims

1. - multiple gelling agents; - Water; a pH adjuster; Preservatives and optionally Flavorings and 1. A basic gel formulation in accordance with the International Dysphagia Diet Standardization Initiative (IDDSI) 2019 edition, wherein the plurality of gelling agents comprises: - Agar and; - alginate as the primary gelling agent; - Low methoxy pectin, 1. A basic gel formulation comprising:

2. The gelling agent comprises, based on the total weight of the base gel: Table 1 10. The base gel formulation of claim 1, wherein the base gel is present in an amount by weight of:

3. The gelling agent comprises, based on the total weight of the base gel: Table 2 is present in an amount by weight of The gel is a gel of texture 1 as defined by the IDDSI flow test standard; 3. The basic gel formulation of claim 2.

4. The gelling agent comprises, based on the total weight of the base gel: Table 3 is present in an amount by weight of The gel is a texture 2 gel as defined by the IDDSI flow test standard.

3. The basic gel formulation of claim 2.

5. The gelling agent comprises, based on the total weight of the base gel: Table 4 is present in an amount by weight of The gel is a texture 3 gel as defined by the IDDSI flow test standard.

3. The basic gel formulation of claim 2.

6. The gelling agent comprises, based on the total weight of the base gel: Table 5 is present in an amount by weight of The gel is a texture 4 gel as defined by the IDDSI flow test standard.

3. The basic gel formulation of claim 2.

7. 7. The basic gel formulation of claim 1, wherein the divalent ion is a calcium ion.

8. 8. The base gel formulation of claim 7, wherein the calcium ions are present as calcium gluconate.

9. 9. The basic gel formulation of any one of claims 1 to 8, wherein the pH adjusting agent maintains a pH between 4 and 6.

10. 10. The basic gel formulation of claim 9, wherein the pH adjuster is sodium hydroxide or citric acid.

11. 11. The basic gel formulation of any one of claims 1 to 10, wherein the preservative is potassium sorbate.

12. 6. The basic gel formulation of any one of claims 2 to 5, packaged in a container that facilitates ingestion of the contents of said container by swallowing or sucking.

13. 13. The basic gel formulation of claim 12, wherein the container is a pouch, sachet, or straw.

14. 6. A method of providing a patient with dietary and / or medicinal ingredients, the method comprising incorporating the ingredients into a basic gel formulation according to any one of claims 2 to 5 and allowing the patient to swallow the formulation.

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