WO2019121517A1

WO2019121517A1 - Powderous formulations

Info

Publication number: WO2019121517A1
Application number: PCT/EP2018/085208
Authority: WO
Inventors: Andrea Hitzfeld; Christa Luise ROLKE; Christian Schaefer; Dirk Oliver WOERNE; Thomas Zwick
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2017-12-20
Filing date: 2018-12-17
Publication date: 2019-06-27
Anticipated expiration: 2020-06-20

Abstract

The present invention relates to a new and improved solid (powderous) formulation, which comprises a high amount of curcuminoids.

Description

Powderous Formulations

Curcuminoids are found in the turmeric plant. Turmeric ( Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae.

The plant is native to the Indian Subcontinent and Southeast Asia. The turmeric powder, which consists of approximately 60-70% carbohydrates, 6- 13% water, 6-8% protein, 5-10% fat, 3-7% dietary minerals, 3-7% essential oil, s, 2-7% dietary fiber, and 1-6% curcuminoids, is very often used in any kind of formulations. (K.M. Nelson et al, J. Med, Chem. 2017, 60, 1620 - 1637). It is used as such or in a formulation.

All percentages in the context of the present patent application, if not otherwise defined, are based on weight.

The content of curcuminoids in turmeric powder is very low (between 1 - 6 %).

The curcuminoids are the following group of compounds of formulae (I), (G), (II) and (III):

The compounds of formulae (I) and (G), which are tautomers, are called curcumin and they are the main components of the curcuminoids and present in an amount of 60 - 80%. The compound of formula (II), which name is demethoxycurcumin is present in an amount of 15 - 27% and the compound of formula (III), which name is bisdemethoxycurcumin is present in an amount of 2 - 15%. The exact composition can vary a lot.

In the context of the present invention the terms curcuminoid or curcuminoids is always related to the mixture of the 4 different compounds of formula (I), (I’), (II) and (III) as disclosed above. As stated the

The main component of the mixture of the curcuminoid is curcumin (present in its keto- or enol-form) is a bright yellow compound in its powderous form. The color of the curcuminoids is pH dependent (yellow at acidic pH, under alkaline conditions soluble and red). The curcuminoids (as well as the turmeric powder) is used as herbal supplement (Ayurvedic medicine), dietary supplement, cosmetics ingredient, food flavoring, and food coloring. As a food additive for gold-orange coloring its E number is E100.

In the prior art only low concentrated formulation comprising turmeric powder are known.

Due to its relevance (especially in food coloring), there is always a need to provide improved formulations of curcuminoids. An important aim was to obtain high concentrated and nevertheless storage stable formulations of curcuminoids.

The present invention relates to a solid formulation of curcuminoids, wherein the content of the curcuminoid is at least 10 wt-%, based on the total weight of the solid formulation.

The solid formulation according to the present invention is very storage as such (in its powder form) as well has very nice properties when used as coloring ingredient in liquid (or gel-like) application forms.

Therefore, the present invention relates to a solid formulation (SF) comprising

(i) at least 10 wt-%, based on the total weight of the solid formulation, of curcuminoid, and

(ii) up to 90 wt-%, based on the total weight of the solid formulation, of at least one protective colloid.

The percentages of a solid formulation according to the present invention always add up to 100%.

The content of the curcuminoid is usually 10 - 30 wt-%, based on the total weight of the solid formulation (preferably 10 - 25 wt-%).

Therefore, the present invention relates to a solid formulation (SF1 ), which is the solid formulation (SF), comprising 10 - 30 wt-%, based on the total weight of the solid formulation (preferably 10 - 25 wt-%) of curcuminoid. The curcuminoids are available as an extract from the turmeric plant from various suppliers (e.g. BioActives Europe GmbH). Most of these extracts have content of the curcuminoids of over 90 %.

The solid formulation comprises 70 wt-% - 90 wt-%, preferably 75 - 90 wt-%, based on the total weight of the solid formulation, of at least one protective colloid.

Therefore, the present invention relates to a solid formulation (SF2), which is the solid formulation (SF) or (SF1 ), comprising 10 - 30 wt-%, based on the total weight of the solid formulation (preferably 10 - 25 wt-%) of at least one protective colloid.

Preferably, the protective colloids in the formulations of the present invention are modified starches or mixtures of modified starches with sugars such as sucrose.

Therefore, the present invention relates to a solid formulation (SF3), which is the solid formulation (SF), (SF1 ) or (SF2), wherein the protective colloids are modified starches or mixtures of modified starches with sugars such as sucrose.

In contrast to starches (non-modified starches) which are hydrophilic and therefore do not have emulsifying capacities, modified starches do have emulsifying capacities. Modified starches are e.g. made from starches substituted by known chemical methods with hydrophobic moieties. For example, starch may be treated with cyclic dicarboxylic acid anhydrides such as succinic anhydrides, substituted with a hydrocarbon chain (see O. B. Wurzburg (editor), "Modified Starches: Properties and Uses, CRC Press, Inc. Boca Raton, Fla., 1986 (and subsequent editions). A particularly preferred modified starch of this invention has the following formula

wherein

St is a starch,

R is an alkylene radical and

R' is a hydrophobic group.

Preferably R is a lower alkylene radical such as dimethylene or trimethylene. R' may be an alkyl or alkenyl group, preferably having 5 to 18 carbon atoms. A preferred compound of formula (I) is an "OSA-starch" (starch sodium octenyl succinate). The degree of substitution, i.e. the number of esterified hydroxyl groups to the number of free non-esterified hydroxyl groups usually varies in a range of from 0.1 percent to 10 percent, preferably in a range of from 0.5 percent to 4 percent, more preferably in a range of from 3 percent to 4 percent.

Therefore, the present invention relates to a solid formulation (SF4), which is the solid formulation (SF), (SF1 ), (SF2) or (SF3), wherein the protective colloid is a modified starch of formula

wherein

St is a starch,

R is an alkylene radical and

R' is a hydrophobic group.

The term "OSA-starch" denotes any starch (from any natural source such as corn, waxy maize, waxy corn, wheat, tapioca and potato or synthesized) that was treated with octenyl succinic anhydride (OSA). The degree of substitution, i.e. the number of hydroxyl groups esterified with OSA to the number of free non-esterified hydroxyl groups usually varies in a range of from 0.1 percent to 10 percent, preferably in a range of from 0.5 percent to 4 percent, more preferably in a range of from 3 percent to 4 percent. OSA-starches are also known under the expression "modified food starch".

These OSA-starches may contain further hydrocolloids, such as starch, maltodextrin, carbohydrates, gum, corn syrup etc. and optionally any typical emulsifier (as co- emulsifier), such as mono- and diglycerides of fatty acids, polyglycerol esters of fatty acids, lecithins, sorbitan monostearate, and plant fibre or sugar.

The term "OSA-starches" encompasses also such starches that are commercially available from various suppliers under the tradenames such as HiCap 100, Capsul, Capsul HS, Purity Gum 2000, UNI-PURE, HYLON VII or C^*EmCap.

It is also possible to use mixtures of modified starches, especially mixtures of OSA- starches.

The terms "modified starches" and "OSA-starches" encompass further also modified starches/OSA-starches that were partly hydrolysed enzymatically, e.g. by glycosylases (EC 3.2; see http://www.chem.qmul.ac.uldiubmb/enzyme/EC3.2/) or hydrolases, as well as to modified starches/OSA-starches that were partly hydrolysed chemically by know methods. The terms "modified starches" and "OSA-starches" encompass also modified starches/OSA-starches that were first partly hydrolysed enzymatically and afterwards additionally hydrolysed chemically. Alternatively, it may also be possible to first hydrolyse starch (either enzymatically or chemically or both) and then to treat this partly hydrolysed starch with cyclic dicarboxylic acid anhydrides such as succinic anhydrides, substituted with a hydrocarbon chain, preferably to treat it with octenyl succinic anhydride.

It is possible to provide solid formulations with less than 5 wt-% of OSA starch (also with less than 4.5 wt-%).

The novel formulations of this invention may further contain adjuvants and/or excipients such as one or more of a mono- di-, oligo- or polysaccharide, a triglyceride, a water-soluble antioxidant, a fat-soluble antioxidant, humectants such as glycerol, sorbitol, polyethylene glycol, propylene glycol, extenders and solubilizers., silicic acid, Ca-silicate, Ca-carbonate and water. Therefore, the present invention relates to a solid formulation (SF5), which is the solid formulation (SF), (SF1 ), (SF2), (SF3) or (SF4), wherein solid formulation further comprises at least one adjuvant and/or at least one excipient.

Therefore, the present invention relates to a solid formulation (SF5’), which is the solid formulation (SF5), wherein the at least oneadjuvant and/or at least one excipients is chosen from the group consisting of mono- di-, oligo- or polysaccharide, triglyceride, water-soluble antioxidant, fat-soluble antioxidant, humectants, extenders, solubilizers., silicic acid, Ca-silicate, Ca-carbonate and water.

Examples of mono- and disaccharides which may further be present in the formulations of the present invention are saccharose, invert sugar, glucose, fructose, xylose, lactose and maltose. Examples of oligo- or polysaccharides which may further be present in the compositions of the present invention are xanthan gum, acacia gum, OSA modified acacia gum, pectins, guar, caroub gums, alginates, celluloses, cellulose derivatives like carboxymethylcellulose, starch, modified starch and starch hydrolysates, such as dextrins and maltodextrins, especially such in the range of 5- 65 dextrose equivalents (hereinafter: DE) and glucose syrup, especially such in the range of 20-95 DE. The term“dextrose equivalent” (DE) denotes the degree of hydrolysation and is measure for the amount of reducing sugar calculated as D- glucose based on dry weight. Native starch has DE close to 0 while glucose has a DE = 100.

The triglyceride is suitably a vegetable oil or fat, such as corn oil, sunflower oil, soybean oil, safflower oil, rape seed oil, peanut oil, arachis oil, palm oil, palm kernel oil, cotton seed oil or cocos oil.

The water-soluble antioxidant may be ascorbic acid and salts thereof, e.g., sodium ascorbate, and the like. The fat-soluble antioxidant may be a tocopherol, e.g., dl-a- tocopherol (i.e., synthetic tocopherol), d-a-tocopherol (i.e., natural tocopherol), b- and g-tocopherol and mixtures thereof; ascorbic acid esters of fatty acids such as ascorbyl palmitate or stearate; butyl hydroxy toluene (BHT); butyl hydroxy anisol (BHA); propyl gallate; or t-butyl hydroxy quinoline. The curcuminoids in the formulation according to the present invention usually have an average particle size below 5miti.

All particle sizes are determined by laser diffraction technique using a "Master-sizer 3000" of Malvern Instruments Ltd., UK. Further information on this particle size characterization method can e.g. be found in "Basic principles of particle size analytics", Dr. Alan Rawle, Malvern Instruments Limited, Enigma Business Part, Grovewood Road, Malvern, Worcestershire, WR14 1XZ, UK and the "Manual of Malvern particle size analyzer". Particular reference is made to the user manual number MAN 0096, Issue 1.0, Nov. 1994. If nothing else is stated all particle sizes referring are Dv50 values (volume diameter, 50% of the population resides below this point, and 50% resides above this point) determined by laser diffraction.

Therefore, the present invention relates to a solid formulation (SF6), which is the solid formulation (SF), (SF1 ), (SF2), (SF3), (SF4), (SF5) or (SF5’), wherein the curcuminoids in the formulation have an average particle size (Dv50) below 5mΐti.

Usually the average particle size (Dv50) is from 100nm to 5mΐti (preferably from 100nm - 1 pm)

Therefore, the present invention relates to a solid formulation (SF7), which is the solid formulation (SF), (SF1 ), (SF2), (SF3), (SF4), (SF5), (SF5’) or (SF6), wherein the curcuminoids in the formulation have an average particle size (Dv50) of from 100nm to 5pm (preferably from 100nm - 1 pm).

The overall size and the shape of the particle of the solid formulation are not relevant for the invention. The same applies for the shape of the particles of the curcuminoids.

The solid formulations (SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and (SF7) are produced using well-known production technology, such as spray drying, granulation, agglomeration. As stated above these formulations are (as such) storage stable for a long time (months). This means that the content of curcuminoids is not decreasing significantly.

The solid formulations (SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and (SF7) can be used as such or in any kind of application forms. They can be mixed into an application form or also used as a part of a coating system (such as the coating of a chocolate lens)

The solid formulations (SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and (SF7) are used in food products, feed products, dietary supplements, personal care and/or pharmaceutical products.

The solid formulations (SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and (SF7) are used in the production of food products, feed products, dietary supplements, personal care and/or pharmaceutical products.

A preferred embodiment of the present invention is the use of at least one solid formulation SF), (SF1 ) (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and/or (SF7) in a non-pasteurised beverage.

Another preferred embodiment of the present invention is the use of at least one solid formulation SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and/or (SF7) in a coating of a chocolate lens.

The present invention also related to food products, feed products, dietary supplements, personal care and/or pharmaceutical products comprising at least one solid formulations (SF), (SF1 ), (SF2), (SF3), (SF3’), (SF4), (SF5), (SF5’), (SF6) and (SF7).

The amount of the solid formulation in any of the above-mentioned application forms, depends on the application as well as of the concentration of the curcuminoids in the solid formulations. It can very a lot. A further important aspect of the present invention is that the formulations according to the present invention are resulting in very stable application forms. These applications forms do have good properties regarding light stability. The following examples illustrate the present invention.

All the parts and percentages in the Examples are related to the weight (when not otherwise stated) and the temperature is given in °C (when not otherwise stated).

Examples

General procedure:

All of the following examples were made according to the following procedure:

The matrix was prepared by dispersing the modified starch (E1450, E1442), sucrose, maltodextrin and gum arabic in deionized water at 65 °C for at least 1 hour. The curcumin extract (Curcuma Longa extract from BioActives Europe GmbH) was added and dispersed, resulting in a raw suspension. Raw suspension was run through a laboratory ball mill (Dispermat SL 12 M1 , VMA-Getzmann GmbH) in circulation mode for 4 hours. Sodium ascorbate or ascorbic acid were added to the milled suspension and if needed pH was lowered to 3.5 by use of sulfuric acid.

Subsequently, milled suspension was spray dried with a laboratory spray dryer (Mobile Minor, GEA Niro). Optionally, spray dried powder was granulated with a lab scale fluid bed processor (Type WFP-Mini, DMR Prozesstechnologie GmbH).

Examples 1 - 5:

All of these solid formulations (Examples 1 - 5) can comprise a small amount of water (due to its production process). The content is less than 5 wt-%.

All of these solid formulations (Examples 1 - 5) are storage stable for significant time under normal storage conditions.

Properties of the solid formulation of Examples 1 - 5:

Particle sizes of milled suspensions (of the curcuminoids) (Dv50):

Exp.1 : 0.47 pm

Exp.2: 0.51 pm

Exp.3: 0.51 pm

Exp.4: 0.43 pm

Exp.5: 0.60 pm

Coloration properties (for 5 ppm curcuminoids in aqueous dilution (solution))

An adequate amount of the formulation is dispersed (to obtain a 5 ppm concentration), dissolved and/or diluted in/with water by use of ultrasonic in a water bath of 50 to 55°C. The resulting "solution" is diluted to a final concentration of the fat-soluble active ingredient of 10 ppm and its UV/VIS-spectrum is measured against water as reference. From the resulting UV/VIS spectrum the absorbance at the specified wavelength of maximum or shoulder, Amax, is determined. Furthermore, the absorbance at 650 nm, A650, is determined. The color intensity E1/1 is the absorbance of a 1 % solution and a thickness of 1 cm and is calculated as follows: E1/1 = (A_max-A65o)^*dilution factor / (weight of sample ^* content of product form in %).

Furthermore, the solid formulations were tested in non-pasteurized soft drinks. The following base formulation was used for all of the following non-pasteurized soft drinks

Table: Base formulation of the soft drink

The solid formulations of each of the Examples were added to this base soft drink formulation that 10ppm of curcuminoid content was obtained.

The so formulated soft drink was tested in a light box as well as in a suntester

Light box experiments

A soft drink was prepared (base formulation above) with a content of 10ppm of curcuminoids The most realistic way to assess the quality of a soft drink is to mimic supermarket conditions with artificial light and day/night rhythm. Therefore, the soft drinks beverages were stored at room temperature under controlled light conditions in a light box.

The light box was set up by employing the following parameters:

Light exposure time: 12hours/day

Light exposure intensity: 800 Lux

Light color: warm white Results

Suntester experiments

A soft drink was prepared (base formulation above) with a content of 10ppm of curcuminoids.

The screening was carried out in the ATLAS SUNTEST® XLS+

The following testing conditions were applied:

Color values were measured before and after light exposure and the color loss dE^* calculated.

Results

It can be seen that the formulations according to the present invention show excellent properties and stabilites.

Claims

1. A solid formulation comprising

(ii) up to 90 wt, based on the total weight of the solid formulation, of at least one protective colloid.

2. The solid formulation according to claim 1 , wherein the protective colloids are modified starches or mixtures of modified starches with sugars such as sucrose.

3. The solid formulation according to claim 2, wherein the modified starch has the following formula

wherein

St is a starch,

R is an alkylene radical and

R' is a hydrophobic group.

4. The solid formulation according to anyone of the preceding claims, wherein the formulation contains further adjuvants and/or excipients.

5. The solid formulation according to anyone of the preceding claims, wherein the curcuminoids have an average (Dv50) particles size of from 100nm to 5pm.

6. Use of at least one solid formulation according to anyone of claim 1 - 5 in food products, feed products, dietary supplements, personal care and/or pharmaceutical products.

7. Food products, feed products, dietary supplements, personal care and/or pharmaceutical products comprising at least one solid formulation according to anyone of claim 1 - 5.