Patent Application
20240156735
This invention generally relates to the field of pharmaceutics, and more specifically relates to formulations of beta-hydroxybutyrate (BHB) salt granules and methods for preparing or producing beta-hydroxybutyrate (BHB) salt granules.
Nutritional, or therapeutic, ketosis is the physiological state of elevated blood ketone body levels resulting from ketogenic diets, calorie restriction, therapeutic fasting and/or supplementation with ketogenic precursors. When in ketosis. the body is essentially burning fat for its primary fuel, and begins cleaving fats into fatty acids and glycerol and transforms the fatty acids into acetyl CoA molecules, which are then eventually transformed through ketogenisis into ketone bodies beta-hydroxybutyrate (beta-hydroxybutyrate or “BHB”), acetoacetate (acetylacetonate), and acetone in the liver. BHB and acetoacetate are the ketone bodies used by the body for energy while acetone is removed as a by-product of ketogenesis. Ketone bodies represent alternative energy substrates for both peripheral tissues and the central nervous system.
While there are many health benefits associated with ketosis, it is challenging to pursue or maintain a state of ketosis. Beta-hydroxybutyrate (BHB) salts are pharmaceutics or supplements that contain a ketone (BHB) bound to a mineral. When these BHB salts are consumed, the salt may dissociate into its individual ions and release BHB, which then raises circulating concentrations of BHB in the blood, thereby promoting or sustaining the ketosis state. Notably, conventional BHB salts are as small as dust, and causes many troubles and problems when being processed by downstream manufacturers. In particular, the issues for conventional production methods of BHB salts include, e.g., problem of dust, repeated or prolonged inhalation of dust by workers, high material consumption, and industrial/environmental pollutions.
To overcome these drawbacks, it is therefore desired to have improved BHB salt products, and production methods thereof, with desired form and uniform particle size, to effectively solve the problem of dust, reduce material consumption, reduce industrial pollutions, and reduce the repeated or prolonged inhalation of dust problem of BHB salts.
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.
This invention generally relates to formulations of BHB salt granules, and methods for producing such BHB salt granules. Particularly, the BHB salt granules according to the present invention have uniform particle size and can effectively solves problem of dust, reduces material consumption, reduces industrial or environmental pollutions, and/or reduces the repeated or prolonged inhalation of dust in association with BHB salts.
One aspect of this invention relates to a beta-hydroxybutyrate (BHB) salt granule, comprising a BHB salt and a filler.
In some embodiments, the BHB salt granule is made of raw materials comprising (a) the BHB salt with a mass percentage ranging from 10% to 99% and (b) the filler with a mass percentage ranging from 1% to 90%.
In some further embodiments, the BHB salt granule is made of raw materials comprising (a) the BHB salt with a mass percentage ranging from 50% to 99%; and (b) the filler with a mass percentage ranging from 1% to 50%.
In some embodiments, the BHB salt comprises a BHB metal salt. For instance, the BHB metal salt may be formed from potassium, calcium, sodium, magnesium, or a mixture thereof (e.g., a mixture of any two or any three thereof, in any ratio).
In some embodiments, the filler comprises microcrystalline cellulose, lactose, mannitol, starch, pregelatinized starch, sodium carboxymethyl cellulose, resistance dextrin, xanthan gum, gum acacia, guar gum, sodium carboxymethyl starch, cross-linked sodium carboxymethyl starch, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, β-cyclodextrin, or a mixture thereof (e.g., a mixture of any two or any three thereof, in any ratio).
Another aspect of the present invention provides a composition for promoting and/or sustaining ketosis in a mammal (e.g., human), comprising BHB salt granule(s) as described above.
In a further aspect, the prevent invention relates to a method for producing BHB salt granules, wherein the BHB salt granules are prepared by granulation process.
In some embodiments, the production method comprises (a) wet granulation; (b) extrusion; (c) spheronization; and (d) drying.
In some embodiments, the wet granulation comprises: mixing a BHB salt and a filler; and adding a binder solution for wet granulation to obtain a wet material. For instance, the binder may be water.
In some embodiments, the ratio of the filler and binder ranges from 1:1 to 1:1.5, rotating speed of the wet granulator is 100-500 rounds/minute (“r/min”), and/or the feeding speed is 5-15 r/min.
In some embodiments, the extrusion comprises: extruding the wet material obtained in step (a) by the extruder, to obtain strip material with the same diameter. In some further embodiments, the extruder has sieve plate aperture of 0.8-1.2 mm, and/or the screw speed of the extruder is 100-300 r/min.
In some embodiments, the spheronization comprises: sphering the strip materials obtained in step (b) at a high speed through the spheronization device to get granules with the same size and desired roundness. In some further embodiments, the rotation speed of the spheronization device may be 400-800 r/min, and/or the time of spheronization may be 15-60 s.
In some embodiments, the drying step comprising drying the granules prepared in step (c) to obtain the BHB salt granules. In some embodiments, the moisture content of final material is controlled below 3%. In some further embodiments, the drying temperature may be 40-60° C., and/or the drying time may be 15-30 minutes.
In some embodiments, the BHB salts have a uniform particle size. In some embodiments, the BHB salts have a particle size of 10-100 mesh.
In some embodiments, the BHB salt is formed from potassium, calcium, sodium, magnesium, or a mixture thereof.
In some embodiments, the filler comprises microcrystalline cellulose, lactose, mannitol, starch, pregelatinized starch, sodium carboxymethyl cellulose, resistance dextrin, xanthan gum, gum acacia, guar gum, sodium carboxymethyl starch, cross-linked sodium carboxymethyl starch, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, β-cyclodextrin, or a mixture thereof.
Still in some embodiments, the method effectively solves problem of dust, reduces material consumption, reduces industrial or environmental pollutions, and/or reduces the repeated or prolonged inhalation of dust in association with BHB salts.
As used herein, the term “or” is meant to include both “and” and “or.” In other words, the term “or” may also be replaced with “and/or.”
As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The following drawings illustrate by way of example and not limitation. For the sake of brevity and clarity, every feature of a given structure is not always labeled in every figure in which that structure appears. Identical reference numbers do not necessarily indicate an identical structure. Rather, the same reference number may be used to indicate a similar feature or a feature with similar functionality, as may non-identical reference numbers.
Reference will now be made in detail to the preferred embodiments of the invention, examples of which are further illustrated. While the invention will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the invention to these embodiments. To the contrary, the invention is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the invention as defined by the claims. Furthermore, in the detailed description of the present invention, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be obvious to one of ordinary skill in the art that the present invention may be practiced without these specific details. In other instances, well known methods, procedures, components, and other features have not been described in detail as not to unnecessarily obscure aspects of the present invention.
Generally speaking, various embodiments of the present invention provide for formulations of BHB salt granules, which include BHB salts and fillers, as well as methods for producing BHB salt granules, e.g., by granulation. Specifically, the production methods of BHB salt granules according to the present invention may include (a) wet granulation; (b) extrusion; (c) spheronization; and (d) drying.
The present invention may achieve a number of technical advantages. For instance, the particle size of the BHB salt granules prepared according to the present invention can be 10-100 (e.g., 10-40) mesh. Under this particle size, the dust problem of BHB salts can be effectively solved; the materials consumption of BHB salts can be effective reduced; the environmental pollutions of BHB salts can be effectively reduced; and the repeated or prolonged inhalation of dust problem of BHB salts can be effectively reduced. At the same time, the BHB salt granules may maintain the uniform particle size.
The following examples are illustrative of select embodiments of the present invention and are not meant to limit the scope of the invention.
The formulation of BHB salt granules in Example 1 is made of the raw materials with the respective mass percentages, as shown in Table 1 below.
The preparation method of such BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 2 is made of the raw materials with the respective mass percentages, as shown in Table 2 below.
The preparation method of such BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 3 is made of the raw materials with the respective mass percentages, as shown in Table 3 below.
The above-mentioned preparation method of BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 4 is made of the raw materials with the respective mass percentages, as shown in Table 4 below.
The above-mentioned preparation method of BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 5 is made of the raw materials with the respective mass percentages, as shown in Table 5 below.
The above-mentioned preparation method of BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 6 is made of the raw materials with the respective mass percentages, as shown in Table 6 below.
The above-mentioned preparation method of BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 7 is made of the raw materials with the respective mass percentages, as show in Table 7.
The above-mentioned preparation method of BHB salt granules includes the following steps:
The formulation of BHB salt granules in Example 8 is made of the raw materials with the respective mass percentages as shown in Table 8 below.
The above-mentioned preparation method of BHB salt granules includes the following steps:
Although specific embodiments and examples of this invention have been illustrated herein, it will be appreciated by those skilled in the art that any modifications and variations can be made without departing from the spirit of the invention. The examples and illustrations above are not intended to limit the scope of this invention. Any combination of embodiments of this invention, along with any obvious their extension or analogs, are within the scope of this invention. Further, it is intended that this invention encompass any arrangement, which is calculated to achieve that same purpose, and all such variations and modifications as fall within the scope of the appended claims.
All the features disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example of a generic series of equivalent or similar features.
It is to be understood that while the invention has been described in conjunction with the detailed description thereof and accompanying figures, the foregoing description and accompanying figures are only intended to illustrate, and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims. All publications referenced herein are incorporated by reference in their entireties.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/CN2021/076213 | Feb 2021 | WO | international |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CN2021/087134 | 4/14/2021 | WO |
