FR3123652A1 - PROCESS FOR MODIFYING STARCH BY HYDRO-THERMAL TREATMENT, STARCH OBTAINED BY THIS PROCESS AND ITS USES - Google Patents

Abstract

The present invention relates to a process for modifying starch by hydro-thermal treatment, the modified starch obtained by this process and its uses.

Description

PROCESS FOR MODIFYING STARCH BY HYDRO-THERMAL TREATMENT, STARCH OBTAINED BY THIS PROCESS AND ITS USES

FIELD OF THE INVENTION

The present invention relates to a process for modifying starch by hydro-thermal treatment, the modified starch obtained by this process and its uses.

TECHNICAL BACKGROUND

The galenic form of a pharmaceutical composition corresponds to the form given to the latter. It is carefully chosen according to the route of administration, the physico-chemical properties of the active ingredient it contains, the expected action, and the desire to reach a specific site in the body. Other criteria such as patient comfort and age may also be taken into account. Among the most widespread dosage forms, mention may be made of the liquid form and the gel form.

The advantage of liquid forms is that the digestion time is shorter than for solid forms so that they are more quickly absorbed by the body, thus resulting in a rapid and effective release of the active ingredients they contain. contain. Depending on their composition and with regard to the speed of gastric emptying, they can produce a high amplitude plasma peak sometimes used to allow assimilated molecules to play an effective health role. On the other hand, liquids are not very satiating, they have little effect on the feeling of satiety, and they lead to a reduction in the production of saliva (the mouth time being very short) which can cause hormonal dysfunctions as well as disturbances in the digestive tract. .

The advantage of gel forms is that their residence time in the mouth is longer than that of liquids and therefore the enzymes of saliva have more time to carry out physico-chemical interactions. This pre-digestion phase is more effective. The digestion time is fast because the saliva lowers the viscosity by modifying the rheology of the gel. Its residence time in the stomach is short due to rapid gastric emptying. The molecules of interest are then quickly released in the body and can exercise their properties.

However, to benefit from these advantages, it is necessary that the formulation of the gel be chemically compatible with saliva, easily solubilisable with the latter and easily degradable by salivary enzymes, in particular amylase. These conditions are essential in order to be able to benefit from the advantages of the liquid form and oral pre-digestion which will improve the bioavailability of the active ingredients and make it possible to overcome the disadvantages of the gel form, i.e. the low flow along the trachea.

There is therefore a need to have a new galenic form having the advantages of liquid forms and gel forms without however having the disadvantages of the latter.

Surprisingly and unexpectedly, the inventors have found a process making it possible to obtain a new galenic form having the advantages of liquid forms (shorter digestion, rapidly absorbed by the body, rapid and effective release of active principles, plasma peak of high amplitude etc.) and forms of gel (longer stay in the mouth, physico-chemical interactions with saliva, predigestion, etc.) without presenting their respective defects (reduction of saliva production, risk of hormonal dysfunctions, disturbances in the digestive tract, weak flow along the trachea, etc.). The process of the invention therefore makes it possible to obtain a new mode of delivery optimized for the administration of active ingredients and/or nutrients contained in pharmaceutical compositions and/or food supplements, but also their absorption, their bioavailability, their future metabolism and their health potential.

A first object of the invention relates to a process for modifying starch by hydrothermal treatment comprising the following steps:
(1) the preparation of a mixture comprising between 55% and 96% by weight of starch, between 1 and 35% by weight of water, and between 3 and 10% by weight of acid,
(2) heating the mixture obtained in step (1) to a temperature of between 60° C. and 120° C. preferably for a period of between 5 and 60 minutes with stirring,
(3) cooling the mixture heated in step (2) preferably with stirring to room temperature, and
(4) obtaining a modified starch,
the percentages being expressed relative to the total weight of the mixture.

A second object of the invention relates to the modified starch obtained according to the method as defined above in the form of a gel.

A third object relates to a composition comprising:
- modified starch obtained according to the process as defined above, preferably in an amount of between 10 and 96% by weight, preferably between 15 and 85% by weight, more preferably between 20 and 70% and even more preferably between 20 and 50% by weight relative to the total weight of the composition,
- at least one active ingredient, preferably in an amount between 0.01 and 90% by weight, more preferably between 1 and 50% by weight and even more preferably between 5 and 30% by weight relative to the total weight of the composition,
- optionally at least one additive, preferably in an amount between 0.01 and 50% by weight, more preferably between 1 and 40% by weight and even more preferably between 5 and 30% by weight relative to the total weight of the composition.

The invention also relates to the process for preparing the composition as defined above, characterized in that it comprises the following steps:
(1) the preparation of a premix comprising the least one active principle and optionally the at least one additive,
(2) the preparation of a mixture comprising between 55% and 96% by weight of starch, between 1 and 35% by weight of water, and between 3 and 10% by weight of acid, the percentages being expressed by relative to the total weight of the mixture,
(3) heating the mixture obtained in step (2) to a temperature of between 60 and 120° C. preferably for a period of between 5 and 60 minutes with stirring,
(4) cooling the mixture heated in step (3) preferably with stirring to room temperature, and
(5) adding the premix obtained in step (1) during the cooling step (4), preferably when the mixture reaches a temperature of between 10°C and 50°C, preferably between 15 °C and 40°C, more preferably between 20°C and 35°C, and even more preferably between 25°C and 30°C, so as to obtain a composition,
(6) optionally adding at least one gelling agent to the composition obtained in step (5).

The invention also relates to the use of the modified starch obtained according to the process as defined above, for the preparation of pharmaceutical compositions, food supplement compositions and/or food compositions.

DESCRIPTION OF FIGURES

: Photograph of the comparative gel (left) and of the gel obtained according to the method of the invention (right)

: Photograph of the flows of the comparative gel (left) and of the gel obtained according to the process of the invention (right) with an angle of inclination of 45°.

: Photograph of the comparative gel (left) and of the gel obtained according to the process of the invention (right) after having been brought into contact with saliva for 2 minutes at 37°C.

: Photograph of the flows of the comparative gel (left) and of the gel obtained according to the method of the invention (right) with an angle of inclination of 45° after contact with saliva for 2 minutes at 37°C.

: Photograph of the flows of the comparative gel (left) and of the gel obtained according to the method of the invention (right) with an angle of inclination of 75° after contact with saliva for 2 minutes at 37°C.

: Photograph of a gel obtained according to the invention (on the left) and of a starch gel obtained without stirring during the cooling step (comparative on the right)

EXAMPLES

Example 1: Process for preparing a starch gel

A gel according to the invention was prepared as follows:

A mixture comprising 60% by weight of starch, 35% by weight of water and 5% by weight of citric acid (the percentages being expressed relative to the total weight of the composition) was prepared. The mixture was then heated at 120°C for 10 minutes with vigorous stirring at 2000 rpm using the IKA Ultra-Turrax® apparatus. The mixture was then cooled to room temperature with very vigorous stirring at 25,000 rpm using the IKA Ultra-Turrax® apparatus in order to obtain a gel.

The quantities of the reagents are also presented in Table 1 below.

% by weight relative to the total weight of the composition Starch 60% Water 35% Citric acid 5%

Results and conclusion:

A gel exhibiting a pH of 2.9 and a viscosity of 4,400,000 cp (measured with an L4 needle viscometer at a speed of 0.1 rpm) was obtained.

The gel thus obtained:
- has adequate viscosity,
- dissolves in seconds in the oral cavity, preferably in about 5 seconds or less,
- is sensitive to the environmental characteristics of the oral cavity (heat, humidity, pressure exerted between the tongue and the palate, saliva etc.), and
- is chemically compatible with the components of saliva and is sensitive to the action of salivary enzymes.

Once swallowed, the gel behaves like a liquid.

Example 2: Comparison in the mouth

Material and method :

- Starch gel obtained according to the process of the invention: viscosity 12,235 cp (measured with an L3 needle viscometer; speed 5 rpm), pH = 3.24, density 1.1, comprising 28% by weight of starch modified (obtained according to the protocol of Example 1 from 80% by weight of starch, 15.38% by weight of water and 4.62% by weight of acid), 12% of spirulina extract and water (qsp),
- Comparative gel: viscosity 12,240 cp (measured with an L3 needle viscometer; speed 5 rpm), pH=3.23, density 1.1, obtained by simply mixing the compounds listed above without additional treatment,
- Human saliva: volume 8 mL brought into contact with 8 mL of products under study.

- Ratio product under study and human saliva 1/1,
- Contact time before deposit: 2 minutes,
- Temperature: 37°C,
- Pressure: 100 pascals,
- Support: glass plate,
- Inclination: 0°, 45° and 75°,
- Quantity of product deposited: 1 mL,
- Flow time: 3 seconds after tilting.

Results :

1- Sample preparation

1 mL of each product (comparative gel and gel according to the invention) was deposited on a glass plate in the form of a drop. A photograph of the two drops of the gels is presented in (comparative gel on the left and gel according to the invention on the right).

The comparative gel has physicochemical properties identical to the gel obtained according to the method of the invention (viscosity, pH, density).

2- Sample characteristics

Beyond the physico-chemical characteristics, the two products exhibit the same behavior:
- same flow velocity, and
- same grip capacity.

The gels were exposed to a 45° tilt for 3 seconds. The photograph is presented in (comparative gel on the left and gel according to the invention on the right).

After exposure to the same inclination for the same time, the flow velocity of the two gels is identical and the deformation of the drop is identical.

3- Bringing the gels into contact with saliva

The two gels were each brought into contact with saliva for 2 minutes at 37°C. The photograph of the two gels after being brought into contact with saliva for 2 minutes at 37°C is presented in (comparative gel on the left and gel according to the invention on the right).

Although the two gels have the same physico-chemical characteristics, their behavior differs after contact with saliva for 2 minutes at 37°C.

The gel obtained according to the method of the invention exhibits perfect and spontaneous miscibility with saliva, whereas the comparative gel does not manage to mix correctly with saliva despite the time and the heat and pressure applied. Thus, with regard to the comparative gel (unlike the gel according to the invention) the salivary enzymes will have difficulty in initiating the first phases of digestibility.

4- Bringing the gels into contact with saliva followed by a 45° tilt

The two gels were each brought into contact with saliva for 2 minutes at 37° C. and then exposed to a 45° tilt for 3 seconds.

The photograph of the two gels after being brought into contact with saliva for 2 minutes at 37°C followed by an inclination at 45° for 3 seconds is presented in (comparative gel on the left and gel according to the invention on the right).

The observation made during contact with saliva is confirmed when the drops of each mixture (gel according to the invention and saliva on the one hand and comparative gel and saliva on the other hand) are exposed to the inclination.

If the gel obtained according to the process of the invention flows rapidly and homogeneously, the comparative gel exhibits almost zero flow without any miscibility with the saliva which flows separately from the comparative gel.

5- Bringing the gels into contact with saliva followed by a 75° tilt

The two gels were each brought into contact with saliva for 2 minutes at 37° C. and then exposed to a 75° tilt for 3 seconds.

The photograph of the two gels after being brought into contact with saliva for 2 minutes at 37°C followed by an inclination at 75° for 3 seconds is presented in (comparative gel on the left and gel according to the invention on the right).

The behavior of the gels observed previously is confirmed and accentuated when the inclination is increased.

At 75° the comparative gel remains en bloc in the upper part, shows no flow and does not dissolve, the saliva dissociates from the gel and flows independently.

On the contrary, the gel obtained according to the method of the invention flows homogeneously and at the same speed as human saliva.

Findings:

Although having physico-chemical characteristics equivalent to other gels, the gel obtained according to the process of the invention dissolves in a few seconds on contact with the oral cavity and its environment (heat, humidity, pressure exerted between the tongue and the palate, saliva etc.), is compatible with the components of saliva and is sensitive to the action of the enzymes contained in the latter.

Example 3: Comparison of a starch gel obtained according to the invention and a starch gel obtained without stirring during the cooling step (comparative)

A gel according to the invention was prepared according to the protocol of example 1.

In the same way, a starch gel obtained without stirring during the cooling step was obtained.

The results are presented in .

Thus, the gel obtained according to the process of the invention (on the left) has the desired physico-chemical properties while the comparative gel (on the right) is in an almost solid form (a thick and lumpy paste is obtained) and does not have not the desired physico-chemical properties.

Example 4: Compositions comprising the starch gel obtained according to the invention

Preparation of compositions:

The compositions shown in Tables 2 to 4 were prepared.

% by weight relative to the total weight of the composition Function Starch 18.2 Texture Agent Water 3.5 Citric acid 1.05 Water 22.75 Harpagophytum root extract 6 Active principles Aqueous extract of turmeric 15 Glucosamine 0.315 Vitamins b12, b9 and b6 (pyridoxamine) 0.01 Calcium lactate 5.5 Lemon flavor 0.03 Mint aroma 0.05 Blackcurrant aroma 0.145 Glutamate 0.8 Green dye 1.3 Dye Granulated sugar 5.2 Sugar Glycerine 20 Conservatives Potassium sorbate 0.05 sodium benzoate 0.1

% by weight relative to the total weight of the composition Function Starch 29.3 Texture Agent Water 3.5 Citric acid 1.05 Water 33.85 Ashwagandha 0.5 Active principles Schizandra fruit 0.5 Magnesium chloride 2.85 Rhodiola root 1.26 Vitamin b9 and b6 (pyridoxamine) 0.01 Caramel flavor 0.013 White tea aroma 0.05 Glutamate 0.8 Granulated sugar 5.2 Sugar Glycerine 19,967 Conservatives Potassium sorbate 0.05 sodium benzoate 0.1 Xanthan 0.2 gelling agents Alginate 0.8

% by weight relative to the total weight of the composition Function Starch 29.3 Texture Agent Water 3.5 Citric acid 1.05 Water 33.85 Melatonin 0.0038 Active principles Angelica root 0.85 Passiflora plant 2 Lemon balm instant leaf 4.68 Magnesium chloride 5.62 Vitamin b6 (pyridoxamine) 0.01 Caramel flavor 0.02 Aroma of anise and liquorice 0.34 Glutamate 0.8 Granulated sugar 5.2 Sugar Glycerine 12.2462 Conservatives Potassium sorbate 0.05 sodium benzoate 0.1 Xanthan 0.3 gelling agents Alginate 0.08

For each of these compositions, a mixture comprising starch, water and citric acid was heated at 120° C. for 10 minutes with vigorous stirring at 2000 rpm using the IKA Ultra-Turrax® device. . The mixture was then cooled to room temperature with very vigorous stirring at 25,000 rpm using the IKA Ultra-Turrax® apparatus to obtain a gel.

A premix comprising the other constituents (except the gelling agents if present) was then added to the gel obtained previously at 25°C with vigorous stirring at 2000 rpm using the IKA Ultra-Turrax® apparatus.

The optional gelling agents such as xanthan and alginate were then added to the previous composition at 25°C with vigorous stirring at 2000 rpm using the IKA Ultra-Turrax® device.

Conclusion :

Beyond dissolving in a few seconds in contact with the oral cavity and their environment (heat, humidity, pressure exerted between the tongue and the palate, saliva etc.), being compatible with the components of saliva, and to be sensitive to the action of the enzymes contained in the saliva, the starch gel obtained according to the method of the invention facilitates the delivery of the active substances contained in the compositions, participates in the plasma peak necessary for the activity of the principles active ingredients, improves metabolic fate and significantly increases the health potential of ingested substances.

Claims (10)

Process for modifying starch by hydrothermal treatment comprising the following steps:
(1) the preparation of a mixture comprising between 55% and 96% by weight of starch, between 1 and 35% by weight of water, and between 3 and 10% by weight of acid,
(2) heating the mixture obtained in step (1) to a temperature of between 60° C. and 120° C. preferably for a period of between 5 and 60 minutes with stirring,
(3) cooling the mixture heated in step (2) preferably with stirring to room temperature, and
(4) obtaining a modified starch,
the percentages being expressed relative to the total weight of the mixture. Process according to Claim 1, characterized in that the starch used in stage (1) is a native starch. Process according to claim 1 or 2, characterized in that the starch is chosen from the group consisting of corn starch, waxy corn starch, wheat starch, potato starch, pea starch, cassava starch, rice starch, and mixtures thereof, preferably corn starch and waxy corn starch and mixtures thereof. Process according to any one of the preceding claims, characterized in that the acid is chosen from the group consisting of citric acid, lactic acid, salicylic acid, formic acid, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, paratoluenesulfonic acid, acrylic acid, capric acid, lauric acid, tridecyl acid, myristic acid, l palmitic acid, stearic acid, behenic acid, ferulic acid, oxalic acid, succinic acid, tartaric acid, malic acid, ascorbic acid, and mixtures thereof, preferably citric acid. Process according to any one of the preceding claims, characterized in that the pH of the composition obtained in step (1) is between 1 and 6, preferably between 2 and 5, and even more preferably between 2.5 and 3.5. Process according to any one of the preceding claims, characterized in that the agitation during the cooling step is dispersion agitation. Modified starch obtained according to the process as defined according to any one of Claims 1 to 6, characterized in that it is in the form of a gel. Composition comprising:
- modified starch obtained according to the process as defined according to any one of claims 1 to 6, preferably in an amount of between 10 and 96% by weight, preferably between 15 and 85% by weight, more preferably between 20 and 70% and even more preferably between 20 and 50% by weight relative to the total weight of the composition,
- at least one active ingredient, preferably in an amount between 0.01 and 90% by weight, more preferably between 1 and 50% by weight and even more preferably between 5 and 30% by weight relative to the total weight of the composition,
- optionally at least one additive, preferably in an amount between 0.01 and 50% by weight, more preferably between 1 and 40% by weight and even more preferably between 5 and 30% by weight relative to the total weight of the composition. Process for preparing the composition as defined according to Claim 8, characterized in that it comprises the following steps:
(1) the preparation of a premix comprising the least one active principle and optionally the at least one additive,
(2) the preparation of a mixture comprising between 55% and 96% by weight of starch, between 1 and 35% by weight of water, and between 3 and 10% by weight of acid, the percentages being expressed by relative to the total weight of the mixture,
(3) heating the mixture obtained in step (2) to a temperature of between 60 and 120° C. preferably for a period of between 5 and 60 minutes with stirring,
(4) cooling the mixture heated in step (3) preferably with stirring to room temperature, and
(5) adding the premix obtained in step (1) during the cooling step (4), preferably when the mixture reaches a temperature of between 10°C and 50°C, preferably between 15 °C and 40°C, more preferably between 20°C and 35°C, and even more preferably between 25°C and 30°C, so as to obtain a composition,
(6) optionally adding at least one gelling agent to the composition obtained in step (5). Use of the modified starch obtained according to the process as defined according to any one of Claims 1 to 6, for the preparation of pharmaceutical compositions, food supplement compositions and/or food compositions.