CN110974843A - Composition and application thereof in balancing NO producing bacteria ratio in intestinal flora - Google Patents
Composition and application thereof in balancing NO producing bacteria ratio in intestinal flora Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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Abstract
The composition mainly comprises the following components, by mass, 10% -15% of leek seed polysaccharide, 10% -20% of oyster polysaccharide, 10% -20% of eucommia male flower polysaccharide, 0.03% -0.05% of β -nicotinamide mononucleotide, 10% -20% of ginseng polysaccharide, 10% -20% of ginger polysaccharide and 10% -15% of moringa oleifera leaf polysaccharide.
Description
Technical Field
The application relates to the field of functional foods, in particular to a composition and application thereof in balancing NO producing bacteria ratio in intestinal flora.
Background
Nitric Oxide (NO) is a novel biological information transmitter involved in the physiological regulation of the body as a cellular messenger molecule that regulates the cardiovascular system, the nervous system and immune function. For example, the level of NO release from vascular smooth muscle of the penis may cause the corpus cavernosum to dilate.
Therefore, promoting the secretion of Nitric Oxide (NO) messenger molecules has the function of harmonizing the physiological functions of the body.
Disclosure of Invention
The present invention provides a composition and its use for balancing the ratio of NO producing bacteria in the gut flora, which is intended to provide a composition that promotes the secretion of NO messenger molecules.
The first aspect of the application provides a composition, which mainly comprises the following components in percentage by mass:
10-15% of leek seed polysaccharide, 10-20% of oyster polysaccharide, 10-20% of eucommia male flower polysaccharide, 0.03-0.05% of β -nicotinamide mononucleotide, 10-20% of ginseng polysaccharide, 10-20% of ginger polysaccharide and 10-15% of moringa oleifera leaf polysaccharide.
In some embodiments of the first aspect of the present application, the composition consists essentially of, in mass fractions:
12-14% of leek seed polysaccharide, 13-18% of oyster polysaccharide, 13-18% of eucommia male flower polysaccharide, 0.03-0.05% of β -nicotinamide mononucleotide, 13-18% of ginseng polysaccharide, 12-17% of ginger polysaccharide and 11-13% of moringa oleifera leaf polysaccharide.
The composition provided by the application can balance NO-producing bacteria in intestinal flora under the mutual assistance of various substances. It can regulate bacterial colony of Bacillus bifidus, Lactobacillus, enterobacteria, enterococcus, etc., balance flora in intestinal tract, and part of intestinal bacteria can communicate with NO network in host via metabolite NO.
In some embodiments of the first aspect of the present application, the composition further comprises a pharmaceutically acceptable excipient.
In some embodiments of the present application, the dosage form of the above composition is a dosage form that can be orally administered.
In a second aspect, the present application provides a use of the composition according to the first aspect for the preparation of a medicament for balancing the ratio of NO producing bacteria in the gut flora.
The composition can balance bacteria capable of secreting NO in intestinal tract, thereby improving NO secretion.
In a third aspect, the present application provides a method for preparing a preparation for balancing the ratio of NO producing bacteria in intestinal flora, comprising: mixing a pharmaceutically acceptable excipient with the composition provided in the first aspect of the present application.
In a fourth aspect, the present application provides a use of the composition of the first aspect as described above in the manufacture of a medicament for increasing the content of NO messenger molecules.
The composition has a communication mechanism with NO network in host body by increasing NO secretion amount in intestinal tract.
In a fifth aspect, the present application provides a use of the composition of the first aspect for the preparation of a medicament for the prevention or treatment of sexual dysfunction in male animals including humans.
In a sixth aspect, the present invention provides a method for preparing a formulation for the treatment of sexual dysfunction in male animals including humans, comprising: mixing a pharmaceutically acceptable excipient with the composition provided in the first aspect of the present application.
In a seventh aspect of the present application, there is provided a use of a composition as provided in the first aspect above for the manufacture of a medicament for promoting nitric oxide release from the smooth muscle of the corpus cavernosum of the penis.
The composition provided by the application can improve the relaxation function of the penis smooth muscle, promote the release level of the penis vascular smooth muscle NO, and cause the relaxation of the corpus cavernosum.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions of the embodiments of the present application will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The compositions of the examples of the present application and their use in balancing the proportion of NO producing bacteria in the gut flora are described in more detail below.
The composition mainly comprises the following components in parts by mass:
10-15% of leek seed polysaccharide, 10-20% of oyster polysaccharide, 10-20% of eucommia male flower polysaccharide, 0.03-0.05% of β -nicotinamide mononucleotide, 10-20% of ginseng polysaccharide, 10-20% of ginger polysaccharide and 10-15% of moringa oleifera leaf polysaccharide.
The leek seeds are warm in nature and slightly sweet in taste, have the effects of tonifying kidney and strengthening yang, nourishing liver, securing essence and the like, and are mainly clinically applicable to impotence, cold pain of waist and knees and spermatorrhea, enuresis, frequent micturition, leukorrhagia and the like caused by liver-yang deficiency and kidney-yang deficiency and insecurity of kidney deficiency.
The leek seed polysaccharide has strong antioxidant activity, and the antioxidant capacity is gradually enhanced along with the increase of the polysaccharide concentration in a certain concentration range. As an example, in embodiments of the present application, the mass fraction of leek seed polysaccharide may be 10%, 11%, 12%, 13%, 14% or 15%. The oyster polysaccharide extracted from Concha Ostreae has biological activities of resisting tumor, resisting oxidation, reducing blood lipid, resisting blood coagulation, resisting thrombi, enhancing organism cellular immunity and humoral immunity function, and resisting leukocyte decrease. Illustratively, in embodiments of the present application, the oyster polysaccharide may be present in a mass fraction of 10%, 12%, 13%, 15%, 18%, 19%, or 20%.
The natural active components of the eucommia male flower have the functions of soothing the nerves, tranquilizing and easing pain, and can obviously improve the sleep after being taken for a long time. In addition, the eucommia male flower contains collagen essential to human body, has the effect of promoting muscle development and strengthening, has obvious anti-fatigue effect of active ingredient lignans, and has obvious effect on people who lack exercise for a long time doing indoor work.
The eucommia male flower polysaccharide has good effect of preventing decreased libido, the patients with kidney-yang deficiency are often seen with low adrenal system function, and the eucommia itself has good effect of exciting the pituitary-adrenal cortex system and enhancing the adrenal cortex function.
Illustratively, in the embodiments of the present application, the mass fraction of the eucommia ulmoides male flower polysaccharide may be 10%, 12%, 13%, 15%, 17%, 19%, 20%, or the like.
β Nicotinamide mononucleotide plays an important role in the cellular energy production of humans, and it is involved in the synthesis of intracellular NAD (nicotinamide adenine dinucleotide, an important coenzyme for cellular energy conversion.) As an example, in the examples of the present application, β Nicotinamide mononucleotide can be present at 0.03%, 0.04% or 0.05% by mass.
The biological activity of ginseng polysaccharide is mainly reflected in the influence on immune function and the resulting immune anti-tumor activity. Has the functions of enhancing immunity, promoting hematopoiesis, reducing blood sugar, resisting diuresis, resisting aging, resisting thrombus, resisting bacteria, resisting inflammation, resisting tumor and the like.
Illustratively, in embodiments of the present application, the mass fraction of the ginseng polysaccharide may be 10%, 11%, 13%, 15%, 18%, 19%, or 20%.
The gingerose has anti-fatigue and anti-oxidation effects, and in the embodiments of the present application, the gingerose may be 10%, 11%, 12%, 14%, 15%, 18% or 20% by mass, as an example.
The moringa oleifera leaf polysaccharide has physiological activities of antioxidation, antibiosis, anti-inflammation, immunoregulation and the like. Illustratively, in embodiments of the present application, the mass fraction of moringa oleifera leaf polysaccharide may be 10%, 11%, 12%, 14%, or 15%.
Illustratively, leek seed polysaccharide, moringa oleifera leaf polysaccharide or eucommia ulmoides male flower polysaccharide and the like can be prepared by the following methods:
cleaning and crushing selected plant raw materials, mixing, adding 4-6 times of hot water with the weight of 60-80 ℃, extracting for 3-4 hours, and filtering to obtain an extracting solution; concentrating the extracting solution, and then precipitating with ethanol to obtain crude polysaccharide; subjecting the crude polysaccharide to chromatographic separation and distilled water elution to obtain polysaccharide liquid; concentrating the polysaccharide solution, precipitating with ethanol, and drying to obtain polysaccharide.
It is understood that, in other embodiments of the present application, the leek seed polysaccharide, moringa oleifera leaf polysaccharide, ginger polysaccharide, or eucommia ulmoides male flower polysaccharide, etc. may be extracted by other methods, or obtained commercially, etc.
Through the research of the inventor, the composition consisting of the various substances can balance NO-producing bacteria in intestinal flora in an auxiliary way. Some intestinal bacteria can communicate with the NO network in the host through the metabolite NO.
For example, the composition can restore a rat model of bifidobacteria, lactobacilli decline and enterobacteria, enterococci rise.
The rat model with decreased bifidobacteria, lactobacilli and increased enterobacteria, enterococci secreted less NO, and increased NO following intervention with the composition. Indicating that the content of the protein capable of increasing the secretion of NO messenger molecules.
NO is an important messenger molecule that plays an important role in the reproductive activities of men, such as the involvement of NO in the regulation of reproductive activities such as spermatogenesis, sperm maturation, spermatogonial apoptosis, androgen secretion, impotence, premature ejaculation, etc., and is mainly synthesized by Nitric Oxide Synthase (NOS) widely distributed in the reproductive system.
The composition can promote nitric oxide release from cavernous smooth muscle of penis.
Further, in some embodiments of the present application, the composition further comprises a pharmaceutically acceptable excipient.
By way of example, pharmaceutically acceptable excipients include, but are not limited to, diluents, absorbents, wetting agents, binders, disintegrants, lubricants, colorants, and the like.
Further, in some embodiments of the present application, the dosage form of the composition is one that can be administered orally. For example, powders, tablets, granules, capsules, solutions, emulsions, suspensions, and the like. Alternatively, in other embodiments of the present application, the composition may be in the form of injection or other dosage forms.
The application also provides an application of the composition in preparing a medicine for balancing the proportion of NO producing bacteria in intestinal flora. Belongs to the diagnosis and treatment purposes of non-diseases.
As mentioned above, the composition can balance NO producing bacteria in intestinal flora. Part of intestinal bacteria can metabolize NO to improve the secretion of NO in the intestinal tract.
The application also provides a preparation method of the preparation for balancing the proportion of NO producing bacteria in intestinal flora, which comprises the following steps: mixing pharmaceutically acceptable adjuvants with the above composition.
The application also provides an application of the composition in preparing a medicine for improving the content of NO messenger molecules. Belongs to the diagnosis and treatment purposes of non-diseases.
In summary, NO in the intestinal tract and NO network in the host have a communication mechanism, which can increase the content of NO messenger molecules.
A method of producing an increased level of NO messenger molecules, comprising: mixing pharmaceutically acceptable adjuvants with the above composition.
The application also provides an application of the composition in preparing a medicament for preventing or treating male animal sexual dysfunction including human. Belongs to the diagnosis and treatment purposes of non-diseases.
A method for preparing a preparation for preventing or treating sexual dysfunction of male animals including human beings, comprising: mixing pharmaceutically acceptable adjuvants with the above composition.
The application also provides an application of the composition in preparing a medicament for promoting nitric oxide release from corpus cavernosum smooth muscle. Belongs to the diagnosis and treatment purposes of non-diseases.
The features and properties of the present application are described in further detail below with reference to examples.
Example 1
The embodiment provides a composition, the total amount of the composition is 15g, wherein the mass fraction of the main components of the composition is as follows:
10% of leek seed polysaccharide, 10% of oyster polysaccharide, 10% of eucommia male flower polysaccharide, 0.03% of β -nicotinamide mononucleotide, 10% of ginseng polysaccharide, 10% of ginger polysaccharide and 10% of moringa oleifera leaf polysaccharide.
Example 2
The embodiment provides a composition, the total amount of the composition is 15g, wherein the mass fraction of the main components of the composition is as follows:
15% of leek seed polysaccharide, 20% of oyster polysaccharide, 20% of eucommia male flower polysaccharide, 0.05% of β -nicotinamide mononucleotide, 20% of ginseng polysaccharide, 20% of ginger polysaccharide and 15% of moringa oleifera leaf polysaccharide.
Example 3
The embodiment provides a composition, the total amount of the composition is 15g, wherein the mass fraction of the main components of the composition is as follows:
12% of leek seed polysaccharide, 13% of oyster polysaccharide, 13% of eucommia male flower polysaccharide, 0.03% of β -nicotinamide mononucleotide, 13% of ginseng polysaccharide, 12% of ginger polysaccharide and 11% of moringa oleifera leaf polysaccharide.
Example 4
The embodiment provides a composition, the total amount of the composition is 15g, wherein the mass fraction of the main components of the composition is as follows:
14% of leek seed polysaccharide, 18% of oyster polysaccharide, 18% of eucommia male flower polysaccharide, 0.05% of β -nicotinamide mononucleotide, 18% of ginseng polysaccharide, 17% of ginger polysaccharide and 13% of moringa oleifera leaf polysaccharide.
Test example 1
Acute toxicity test in small animals
Test animals: NOD/SCID mice (SPF grade) with a body weight of 22-26 g, male and female halves, provided by Nanjing university.
Number of use license: SYXK 2014-0023
The method and the result are as follows: 48 mice were divided into 4 groups of 12 mice each. Before the test, the mice are fasted/forbidden for 6 hours, the oral dosage is 0.2g/mL, the composition provided in example 1 is subjected to intragastric gavage for 0.2g, 0.4g, 0.6g and 0.8g within 24 hours according to A, B, C, D groups respectively, and the NOD/SCID mice are observed to have normal activity, no abnormal general state and no observable toxic reaction within 1 week. Indicating that the highest dose is still within the safe range when converted to 40g/kg body weight.
Test example 2
Long term toxicity test in small animals
Test animals: NOD/SCID mice (SPF grade) with a body weight of 22-26 g, male and female halves, provided by Nanjing university.
Number of use license: SYXK 2014-0023
The method and the result are as follows: 48 mice were divided into 4 groups of 12 mice each. Fasting and water prohibition are carried out for 6 hours before the test, the oral dosage is 0.2g/mL, the stomach is gavaged within 24 hours according to A, B, C groups, 0.1g, 0.2g and 0.3g are respectively gavaged within 24 hours, the group D is normally fed as a control group, after continuous feeding for 8 weeks, euthanasia is carried out at the end point of the test, a tissue sample is taken and observed; during the period, NOD/SCID mice normally move, the general state is not abnormal, and the tissue observation results are as follows: compared with the control group, the gavage group has no obvious change and no observable toxic reaction. The dosage range obtained by weight conversion is still within the safe range relative to the clinical dosage of 60-120 times.
Test example 3
NO level test
Test animals: kunming mice (SPF grade) with a body weight of 24-30 g in male and female pairs, provided by Nanjing university. Number of use license: SYXK 2014-0023.
The method comprises the following steps: 48 mice were divided into 4 groups of 12 mice each, and the mice were divided into groups after adaptive feeding. Except for normal control group mice, the gastric antibiotic-metronidazole (10-20mg/mL) simulates an intestinal dysbacteriosis model for 7 days continuously.
Grouping: the different test items were given in groups starting at week 2 for 14 days. Table 1 shows the experimental animal group feeding situation, wherein the composition group was supplied with the composition provided in example 1.
TABLE 1 Experimental animals group rearing situation
At the end of the experiment, the mouse picks up eyeballs and takes blood, and serum is separated after centrifugation at 4000 Xg for 10min and is subpackaged to be at minus 86 ℃ for storage. After blood collection, mice are killed by cervical dislocation, and cecum contents are collected aseptically for later use.
Collecting fresh caecum content, weighing sterile normal saline 50 times the weight of the fresh caecum content to prepare homogenate, and diluting 10 times by 10 times gradient6And (3) doubling, coating on a selective medium, and carrying out constant-temperature culture for 36h to identify and count the number of colonies (log10CFU/g), and the results are shown in tables 2 and 3.
TABLE 2 detection of the content of Enterobacter and enterococcus in the intestinal tract of each group of mice (log10CFU/g)
TABLE 3 detection of Bifidobacterium and Lactobacillus content in intestinal tract of mice (log10CFU/g)
Note: p < 0.05 compared to normal control group and # p < 0.05 compared to model group.
As can be seen from tables 2 and 3: compared with a normal control group, the intestinal flora of the model group mice is obviously changed, wherein bifidobacteria and lactobacilli are reduced (p is less than 0.05), and the enterobacteria and enterococci are obviously increased, so that the intestinal flora imbalance model of the mice is successfully established. And the number of intestinal flora of the mice intervened by the composition provided by the embodiment 1 is obviously recovered, the number of bifidobacteria and lactobacilli is obviously increased, the number of enterobacteria and enterococci is obviously reduced, and the difference from the model group has statistical significance (# p < 0.05).
The NO content was measured according to the protocol of the Griess kit, and the results are shown in Table 4.
TABLE 4 serum NO content detection (mmol/L) for each group of mice
Note: p < 0.05 compared to normal control group and # p < 0.05 compared to model group.
As can be seen from table 4: compared with the normal control group, the mice in the model group have the obvious change of the intestinal flora, the serum NO level is obviously reduced (p is less than 0.05), and the composition provided by the example 1 has the obvious effect of increasing the serum NO content of the mice (p is less than 0.05) NO matter the normal control group or the control intestinal flora imbalance model group. The composition can promote NO secretion and function by regulating the proportion of NO-producing bacteria in intestinal flora.
In conclusion, the composition provided by the examples of the present application is still within the safe range when the highest dosage is 40g/kg in terms of body weight. The dosage range obtained by weight conversion is still within the safe range when the dosage range is 60-120 times of the clinical dosage. The composition provided by the embodiment of the application can balance intestinal flora of mice, particularly regulate bifidobacterium, lactobacillus, enterobacteria, enterococcus and the like, and further promote NO secretion and exert functions.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims (10)
1. The composition is characterized by mainly comprising the following components in parts by mass:
10-15% of leek seed polysaccharide, 10-20% of oyster polysaccharide, 10-20% of eucommia male flower polysaccharide, 0.03-0.05% of β -nicotinamide mononucleotide, 10-20% of ginseng polysaccharide, 10-20% of ginger polysaccharide and 10-15% of moringa oleifera leaf polysaccharide.
2. The composition according to claim 1, characterized by essentially comprising, in mass fraction:
12-14% of leek seed polysaccharide, 13-18% of oyster polysaccharide, 13-18% of eucommia male flower polysaccharide, 0.03-0.05% of β -nicotinamide mononucleotide, 13-18% of ginseng polysaccharide, 12-17% of ginger polysaccharide and 11-13% of moringa oleifera leaf polysaccharide.
3. The composition of claim 1 or 2, wherein the composition further comprises a pharmaceutically acceptable excipient.
4. The composition according to claim 1 or 2, wherein the composition is in a form that can be administered orally.
5. Use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for balancing the proportion of NO producing bacteria in the gut flora.
6. A preparation method of a preparation for balancing NO producing bacteria ratio in intestinal flora is characterized by comprising the following steps: mixing a pharmaceutically acceptable excipient with the composition of any one of 1 to 4.
7. Use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for increasing the content of NO messenger molecules.
8. Use of a composition according to any one of claims 1 to 4 in the manufacture of a medicament for the prophylaxis or treatment of sexual dysfunction in a male animal, including a human.
9. A process for the preparation of a formulation for the treatment of sexual dysfunction in male animals including humans, comprising: mixing a pharmaceutically acceptable excipient with the composition of any one of 1 to 4.
10. Use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for promoting nitric oxide release from the smooth muscle of the corpora cavernosa.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111557949A (en) * | 2020-05-28 | 2020-08-21 | 深圳爱生生命科技有限公司 | Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof |
| CN115671178A (en) * | 2021-07-22 | 2023-02-03 | 成都川宇健维生物科技有限公司 | Composition comprising beta-nicotinamide mononucleotide and rosa roxburghii tratt extract and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111557949A (en) * | 2020-05-28 | 2020-08-21 | 深圳爱生生命科技有限公司 | Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof |
| CN111557949B (en) * | 2020-05-28 | 2022-08-26 | 深圳爱生生命科技有限公司 | Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof |
| CN115671178A (en) * | 2021-07-22 | 2023-02-03 | 成都川宇健维生物科技有限公司 | Composition comprising beta-nicotinamide mononucleotide and rosa roxburghii tratt extract and application thereof |
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Application publication date: 20200410 |