NL2035081B1 - Composition promoting absorption and utilization of nutrients and intervention factors - Google Patents
Composition promoting absorption and utilization of nutrients and intervention factors Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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Abstract
The present invention provides a composition promoting absorption and utilization of nutrients and intervention factors. The composition has a synergistic effect among respective components, can achieve a good effect by oral administration, and has a broad application prospect. Secondly, according to the present invention, component and formula screening tests 10 are conducted on the composition, an optimal formula is found, and a method for preparing the composition is provided. Finally, according to the present invention, other uses of the composition are further explored, discovering functions of the composition in improving microcirculation, activating an eNOS, activating a deacetylase, improving mitochondrial functions, and activating a superoxide dismutase, and providing related uses.
Description
COMPOSITION PROMOTING ABSORPTION AND UTILIZATION OF
NUTRIENTS AND INTERVENTION FACTORS
[0001] The present invention relates to the technical field of pharmaceuticals and food, in particular to a composition promoting absorption and utilization of nutrients and intervention factors.
[0002] Nutrients refer to essential substances that can maintain normal physiological functions of the human body, including proteins, fats, carbohydrates, vitamins, minerals, etc. Intervention factors refer to substances that can regulate human body metabolism, antioxidant, anti-inflammatory, anti-aging and other physiological processes, including polyphenol compounds, carotenoids, flavonoid compounds, polyunsaturated fatty acids, etc. The nutrients and intervention factors play an important role in human body health and can prevent and treat a variety of chronic diseases, such as cardiovascular diseases, diabetes, cancers, etc.
[0003] However, there are often some problems with the preparations of nutrients and intervention factors in the current market, such as unstable preparation forms, low bioavailability, etc. For example, the polyphenol compounds have relatively strong antioxidant activity, but they are easily decomposed or combined with other substances
In a gastrointestinal tract, resulting in very low absorption rate and bioavailability. The carotenoids are an important class of lipid-soluble pigments that have anticancer and immunity enhancing effects. However, they are unstable in water-soluble media and are prone to oxidation or aggregation, affecting their biological activity.
[0004] The absorption of nutrients and intervention factors is related to factors such as solubility, stability, and bioavailability in a digestive tract. In order to improve the absorption efficiency of nutrients and intervention factors, some technical means are usually used, such as microencapsulation, nanocrystallization, embedding, etc., to protect nutrients and intervention factors from being damaged by gastric acid or intestinal flora, or to increase the solubility and permeability of nutrients and intervention factors in an intestinal tract.
[0005] However, these technical means often require complex process equipment and high costs, and may affect the activity or safety of nutrients and intervention factors.
Therefore, developing a simple, economical and effective method to promote the absorption of nutrients and intervention factors is an important subject in the field of nutriology and food science.
[0006] In order to solve the above problem, the present invention provides a composition promoting absorption and utilization of nutrients and intervention factors.
The composition provided by the present invention can promote the absorption of nutrients and intervention factors, improve microcirculation, activate an endothelial nitric oxide synthase (eNOS) system, promote blood flow to increase transport and arrival of nutrients and intervention factors, and produce more mitochondria to provide cellular kinetic energy.
[0007] The composition promoting absorption and utilization of nutrients and intervention factors provided by the present invention is composed of four components: a component that promotes absorption, a component that improves microcirculation, a component that activates the eNOS system, and a component that increases mitochondria.
[0008] The component that promotes absorption includes piperine. From a perspective of mechanism, the piperine can inhibit the excretion of nutrients by p-glycoprotein and improve the enzyme activity of a small intestine membrane to promote the absorption of nutrients by an intestinal tract. Through the above mechanism, absorption of nutrients can be improved.
[0009] The component that improves microcirculation includes a blackcurrant extract, whose active ingredient is cycloglycine-proline (cGP). From a perspective of mechanism, the cGP can promote the production of more capillaries to improve microcirculation. Through the above mechanism, the transport and arrival of nutrients can be achieved.
[0010] The component that activates the eNOS system includes a green mangiferin.
From a perspective of mechanism, the green mangiferin can activate the eNOS system to promote blood flow. Through the above mechanism, the transport and arrival of nutrients can be achieved.
[0011] The component that increases mitochondria includes a pyrroloquinoline quinone (PQQ) and a coenzyme Q10. From a perspective of mechanism, the PQQ and the coenzyme Q10 help to produce more mitochondria to improve cellular energy.
Through the above mechanism, the cellular kinetic energy can be provided.
[0012] After complex experiments, we have found that the above compositions have synergistic effects with one another. The effect of the composition is not the sum of the effects of respective components, but rather a significant synergistic effect. The various effects of the composition are several to dozens of times that of a single component to varying degrees.
[0013] In an aspect, the present invention provides a composition promoting absorption and utilization efficiency of nutrients and intervention factors by a human body. The composition includes: a piperine, a blackcurrant extract, a green mangiferin, a PQQ, and a coenzyme Q10.
[0014] Further, in a single part of composition, by weight, an addition amount of the piperine 1s 5 mg; an addition amount of the blackcurrant extract is 20-50 mg; an addition amount of the green mangiferin is 50-100 mg; and a sum of addition amounts of the PQQ and the coenzyme Q10 is 5-20 mg.
[0015] In some embodiments, in a single part of composition, by weight, the addition amount of the piperine is 5 mg; the addition amount of the blackcurrant extract is 50 mg; the addition amount of the green mangiferin is 80 mg; the addition amount of the
PQQ is 5 mg; and the addition amount of the coenzyme Q10 is 5 mg.
[0016] In another aspect, the present invention provides a preparation method for the composition. The preparation method includes two steps of accurate weighing and uniform mixing. A fixed mass of composition can be accurately prepared.
[0017] In another aspect, the present invention provides a use of the above composition in preparing a preparation for improving absorption or utilization of nutrients or intervention factors.
[0018] Further, the nutrients or intervention factors include, but are not limited to, 3- carotene, vitamin B6, curcumin, and resveratrol.
[0019] In another aspect, the present invention provides a use of the above composition in preparing a preparation for improving microcirculation.
[0020] The microcirculation refers to the blood flow and exchange between venules and arterioles at capillaries. The composition provided by the present invention can improve the microcirculation both 1n a short term and in a long term.
[0021] In another aspect, the present invention provides a use of the above composition in preparing a preparation for activating an eNOS system.
[0022] The composition provided by the present invention can activate a nitric oxide synthase and produce nitric oxide in blood vessels to regulate a vascular function and promote blood flow.
[0023] In another aspect, the present invention provides a use of the above composition in preparing a preparation for activating a deacetylase.
[0024] In another aspect, the present invention provides a use of the above composition in preparing a preparation for improving mitochondrial functions.
[0025] The mitochondrial functions include, but are not limited to, mitochondrial respiratory enzyme activity, mitochondrial DNA content, and mitochondrial quantity.
The composition provided by the present invention can improve the mitochondrial respiratory enzyme activity, can increase the mitochondrial DNA content, and can increase the mitochondrial quantity.
[0026] In another aspect, the present invention provides a use of the above composition in preparing a preparation for activating a superoxide dismutase (SOD).
[0027] The present invention has the following beneficial effects:
[0028] 1. A composition promoting absorption and utilization of nutrients and intervention factors is provided, has a synergistic effect among respective components, can achieve a good effect by oral administration, and has a broad application prospect.
[0029] 2. Component and formula screening tests are conducted on the composition, an optimal formula is found, and a method for preparing the composition is provided.
[0030] 3. Uses of the composition are explored, discovering functions of the composition in improving microcirculation, activating an eNOS, activating a 5 deacetylase, improving mitochondrial functions, and activating an SOD, and providing related uses.
[0031] The present invention will be further elaborated in detail by the specification given below and by specific examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention. Test methods used in the following examples are all conventional methods unless otherwise specified; materials, reagents, etc. used can be obtained from commercial sources unless otherwise specified.
[0032] Example 1: Preparation of composition
[0033] In a single part of composition, by weight, an addition amount of a piperine was 5 mg; an addition amount of a blackcurrant extract was 50 mg; an addition amount of a green mangiferin was 80 mg; an addition amount of a PQQ was 5 mg; and an addition amount of a coenzyme Q10 was 5 mg. Sources of the piperine, the blackcurrant extract, the green mangiferin, the PQQ, and the coenzyme Q10 were supplemented.
[0034] Weighing was conducted according to the above amounts, and thorough and uniform mixing was conducted to obtain a composition. A composition with a fixed mass prepared strictly in accordance with the above addition amounts was called one part of composition. Unless otherwise specified, compositions in the following examples referred to one part of composition prepared in this example.
[0035] Example 2: Components of composition
[0036] In a composition provided by the present invention, each component had undergone extensive experimental screening, and a formula of the composition was obtained, and had a synergistic effect. Firstly, we prepared several groups of compositions with different formulas using the method in Example 1, and adopted a double-blind experiment. A control group was orally administrated with 100 mg of vitamin B6. An experimental group was orally administrated with 100 mg of vitamin
B6+composition. Concentrations of serum vitamin B6 were monitored 2 and 4 hours after administration. The concentration could reflect the utilization rate of vitamin B6.
The higher the concentration, the higher the utilization rate, and thus the better the effect of the composition. The concentration of serum vitamin B6 of the experimental group was divided by that of the control group to obtain a multiple relationship.
Results were shown in Table 1.
Table 1: Influence of different compositions on utilization rate of vitamin B6
Piperine Blackcurrant Green PQQ (mg) Coenzyme Ratio at 2 | Ratio at 4
BEES
(mg)
Te
[0037] The results show that each component in the composition produces a synergistic effect on promoting the absorption and utilization of vitamin B6 by the composition, and none of them is dispensable.
[0038] Example 3: Formula of composition
[0039] According to the commonly used doses of respective components in a composition, we first roughly defined a formula range: an addition amount of a piperine was 1-10 mg; an addition amount of a blackcurrant extract was 10-100 mg; an addition amount of a green mangiferin was 30-150 mg; an addition amount of a PQQ was 1-10 mg; and an addition amount of a coenzyme Q10 was 1-10 mg. Through several formula experiments, we found that the effects of compositions were not good at certain addition amounts, and a formula needed to be further screened.
[0040] Firstly, 50 mg of the blackcurrant extract, 100 mg of the green mangiferin, 5 mg of the PQQ, and 5 mg of the coenzyme Q10 were taken as a fixed combination to prepare a reference substance, recorded as reference substance A. On the basis of reference substance A, different amounts of the piperine were added to select an optimal addition amount of the piperine, and different formulas of compositions were prepared. A double-blind experiment was adopted, with 3 volunteers orally administrated with 100 mg of vitamin B6+composition, and the other 3 volunteers orally administrated with 100 mg of vitamin B6+reference substance. Serum vitamin
B6 concentrations were measured before, 2 hours after, and 4 hours after the experiment, respectively. A ratio of the concentration of serum vitamin B6 in an experimental group to that in a control group was calculated under different formulas.
Results were shown in Table 2.
Table 2: Influence of addition amount of piperine on utilization rate of vitamin B6
Addition amount of piperine Experimental-control ratio at 2 | Experimental-control ratio at 4
B
[0041] The results show that as the addition amount of the piperine is gradually increased, the utilization rate of vitamin B6 is gradually increased. The level of increase 1s highest when the addition amount is 5 mg, but the change 1s not significant thereafter. It can be seen from this that the peak addition amount of the piperine is 5 mg. Therefore, the optimal addition amount of the piperine is 5 mg. After 2 hours, the concentration of serum vitamin B6 in the experimental group is 4.5 times that in the control group, and after 4 hours, the concentration of serum vitamin B6 in the experimental group 1s 4.2 times that in the control group. Compared with the composition without added piperine, we can find that adding 5 mg of piperine to the formula has a significant synergistic effect, which is a preferable choice.
[0042] Subsequently, we fixed 5 mg of the piperine, 100 mg of the green mangiferin, 5 mg of the PQQ, and 5 mg of the coenzyme Q10 as a formula, changed the addition amount of the blackcurrant extract, and adopted the same method as above. Results were shown in Table 3.
Table 3: Influence of addition amount of blackcurrant extract on utilization rate of vitamin
B6
Addition amount of Experimental-control ratio at 2 | Experimental-control ratio at 4
[0043] The results show that the optimal addition amount of the blackcurrant extract is 20-50 mg, and the increase in utilization rate of vitamin B6 is not significant after the addition amount exceeds 50 mg. It can be seen that the peak addition amount of the blackcurrant extract is 50 mg. Therefore, the effect 1s best when the addition amount of the blackcurrant extract is 50 mg, and compared with the composition without added blackcurrant extract, it can be found that the blackcurrant extract plays a significant synergistic effect as a component of the composition.
[0044] Subsequently, we fixed 5 mg of the piperine, 50 mg of the blackcurrant extract, 5 mg of the PQQ, and 5 mg of the coenzyme Q10 as a formula, changed the addition amount of the green mangiferin to study the formula addition amount of the green mangiferin, and adopted the same method as above. Results were shown in Table 4.
Table 4: Influence of addition amount of green mangiferin on utilization rate of vitamin B6
Addition amount of green Experimental-control ratio at 2 | Experimental-control ratio at 4
[0045] The results show that the optimal addition amount of the green mangiferin is 50-100 mg, and the increase in utilization rate of vitamin B6 is not significant after the addition amount exceeds 80 mg. It can be seen that the upper limit of the addition amount of the green mangiferin is 80 mg. Therefore, the effect is best when the addition amount 1s 80 mg, and compared with the composition without added green mangiferin, it can be found that the green mangiferin plays a synergistic effect as a component of the composition.
[0046] Subsequently, we conducted the same study on the PQQ and the coenzyme
Q10. Results show that when the sum of the addition amounts of the two 1s 5-20 mg, the effects are good, with the optimal addition amounts of 5 mg of the PQQ and 5 mg of the coenzyme Q 10.
[0047] Example 4: Improvement in absorption of nutrients by composition
[0048] This example used the composition prepared in Example 1 and adopted a double-blind method to study promoting of absorption and utilization of B-carotene, vitamin B6, curcumin and resveratrol by the composition.
[0049] The double-blind method was adopted. Control groups were orally administrated with 2 g of the -carotene, 100 mg of the vitamin B6, 2 g of the curcumin and 500 mg of the resveratrol, respectively. Experimental groups were additionally administrated with one part of composition each time on the basis of the control groups. The concentration change of the above active substances in serum was monitored. Concentration ratios were obtained by dividing the highest concentration of the experimental groups by the highest concentration of the control groups. Results were shown in Table 5.
Table 5: Improvement in absorption of nutrients by composition
Active B-carotene Vitamin B6 Curcumin Resveratrol
El hn
Concentration 11.1 9.1 6.9 28.6 aT tL
[0050] The results show that the composition provided by the present invention can significantly improve the absorption of the above nutrients; in terms of mechanism, the composition inhibits the excretion of nutrients by p-glycoprotein and improves the enzyme activity of a small intestine membrane to promote the absorption of nutrients by an intestinal tract. Therefore, theoretically, the promoting effect of the composition provided by the present invention on absorption of nutrients can be extended to the vast majority of nutrients and intervention factors.
[0051] Example 5: Improvement of microcirculation by composition
[0052] This example used the composition prepared in Example 1. Ten healthy individuals aged between 36 and 64 were recruited as volunteers. Firstly, the microcirculation of the volunteers was observed. A method to observe microcirculation was that strong light was shined on nail folds of ring fingers of left hands of the volunteers, then, the volunteers were orally administrated with one part of composition, and the microcirculation was observed every 15 minutes after oral administration, with four times totally.
[0053] The results show that the blood flow rate between venules and arterioles increases, proving that oral administration of the composition provided by the present invention can significantly improve microcirculation.
[0054] In addition, to verify the long-term effect of the composition provided by the present invention on improving microcirculation, we recruited ten healthy individuals aged between 36 and 64 as volunteers, who were administrated with the composition for three consecutive days, and then the microcirculation levels of the volunteers were observed every other day. It was found that the microcirculation of the volunteers was improved within 12 days after discontinuing the administration. The results show that the composition provided by the present invention has a long-term effect on improving microcirculation,
[0055] Example 6: Activation of deacetylase and eNOS by composition
[0056] The composition provided by the present invention can activate Sirtuin (deacetylase) and eNOS to promote blood flow.
[0057] This example used the composition prepared in Example 1. Ten healthy individuals aged between 36 and 64 were recruited as volunteers. Firstly, blood collection was conducted on the volunteers, then, the volunteers were orally administrated with one part of composition, blood collection was conducted again the second hour after oral administration, and enzyme activity detection was conducted on blood samples by using Epigenase Universal SIRT Activity/Inhibition Assay Kit (Colorimetric), which was purchased from AmyJet Scientific Inc. A detection method was the same as the kit manual.
[0058] The results show that after administrated with the composition provided by the present invention, the volunteers have average deacetylase activity increased fourfold.
The composition provided by the present invention has a significant effect on activating deacetylase.
[0059] Then we used the same method to determine the activation effect of the composition on eNOS by using Nitric Oxide Synthase Activity Assay Kit (Colorimetric) from BioVision, which was purchased from US BioVision. Inc. A detection method was the same as the kit manual.
[0060] The results show that after administrated with the composition provided by the present invention, the volunteers have average deacetylase activity increased threefold.
The composition provided by the present invention has a significant effect on activating eNOS.
[0061] Example 7: Improvement of mitochondrial functions by composition
[0062] Mitochondrial functions improved by the composition provided by the present invention include mitochondrial respiratory enzyme activity, mitochondrial DNA content, and mitochondrial quantity.
[0063] This example used the composition prepared in Example 1, adopted the method as described in Example 6, conducted detection by selecting CheKine™ Mitochondrial
Respiratory Chain Complex I Activity Assay Kit (Colorimetric), which was purchased from Abbkine Scientific Co., Ltd. A detection method was the same as the kit manual.
The mitochondrial DNA content was determined by using absolute quantification PCR method. The mitochondrial quantity was subjected to flow cytometry by using a flow cytometer.
[0064] The results show that after 24 hours of administrating the composition, in blood cells of the volunteers, the mitochondrial respiratory enzyme activity 1s significantly improved, the DNA content is increased, and the mitochondrial quantity is significantly increased. To sum up, after oral administration of the composition of the present invention, the overall mitochondrial functions are significantly improved to provide cellular kinetic energy.
[0065] Example 8: Activation of SOD by composition
[0066] The composition provided by the present invention can activate an SOD, also known as an antioxidant enzyme, to provide an antioxidant function. This example used the composition prepared in Example 1. The method was the same as Example 6.
Blood samples of volunteers before and after oral administration of the composition were obtained, and then the activity of the SOD was determined by using the following method:
[0067] (1) a sufficient number of cells or tissue samples were taken and washed with
PBS three times to remove impurities;
[0068] (2) the samples were processed by using an ultrasonic disperser to break cell membranes and completely release an antioxidant enzyme inside the cells;
[0069] (3) the samples were transferred to centrifuge tubes and centrifuged for 10 minutes using an ultra-low temperature centrifuge to remove residues;
[0070] (4) a certain amount of 10n exchange resin was taken and loaded into a column to fully adsorb the antioxidant enzyme;
[0071] (5) the samples after breaking were slowly dripped into the column to allow the antioxidant enzyme to bind to the resin;
[0072] (6) the antioxidant enzyme on the column was washed with PBS to remove non-specific binding conjugates; and
[0073] (7) the activity of the antioxidant enzyme was measured by using active esterase substrate superoxide anion radicals. The activity of the antioxidant enzyme could be measured by the degradation rate of the substrate.
[0074] The results show that the total activity of the antioxidant enzyme is increased in the blood samples after oral administration of the composition. It can be seen that oral administration of the composition provided by the present invention can activate the antioxidant enzyme to improve the antioxidant function.
[0075] The above examples describe the technical solution of the present invention in detail. It should be understood that the above are only specific examples of the present invention and are not used to limit the present invention. Any amendment, addition or substitution in similar manners made within the principle scope of the present invention should be included in the protection scope of the present invention.
Claims (10)
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