CN109331039B

CN109331039B - Composition for improving nutritional anemia and application thereof

Info

Publication number: CN109331039B
Application number: CN201811602410.8A
Authority: CN
Inventors: 张雅丽; 刘海滨; 张淹; 周祥山; 王春艳; 孙阳恩; 李丽; 李士栋
Original assignee: Dong E E Jiao Co Ltd
Current assignee: Dong E E Jiao Co Ltd
Priority date: 2018-12-26
Filing date: 2018-12-26
Publication date: 2021-07-20
Anticipated expiration: 2038-12-26
Also published as: CN109331039A

Abstract

The invention provides a composition for improving nutritional anemia and application thereof, and relates to the technical field of application of donkey-hide gelatin. The composition comprises the following components in parts by weight: 100-2000 parts of donkey-hide gelatin, 1-20 parts of ferrous fumarate, 0.01-1 part of folic acid, 1-70 parts of cellulose and 2-75 parts of lactose. The composition can obviously increase the body weight of an anemic rat model, increase the content of hemoglobin, improve the hematocrit and reduce the content of free porphyrinogen, and can be used for preparing a medicine or a health-care product for improving nutritional anemia.

Description

Composition for improving nutritional anemia and application thereof

Technical Field

The invention belongs to the technical field of application of donkey-hide gelatin, and particularly relates to a composition for improving nutritional anemia and application thereof.

Background

Iron Deficiency Anemia (IDA) is a condition of subnormal hemoglobin due to iron deficiency, is the most common nutrient deficiency disease, has a high incidence rate in infants and women of childbearing age in developing countries and economically undeveloped areas, and is an important global nutritional problem. According to WHO reports, the incidence rate of iron-deficiency anemia in adult women is 20%, the incidence rate of iron-deficiency anemia in pregnant women is 40%, and the incidence rate of iron-deficiency anemia in children is up to 50%, and the iron-deficiency anemia mainly and clinically shows symptoms of weakness, tiredness, dizziness, physical strength reduction, endurance loss and the like. Women in the childbearing age as high-incidence crowds with iron-deficiency anemia can easily influence the whole reproductive and reproductive process, so that the effective prevention has important medical and social significance.

At present, the treatment means aiming at the iron-deficiency anemia is mainly iron supplement, the curative effect is quick, but gastrointestinal tract stimulation of different degrees exists, and certain damage is caused to the organism after long-term administration. The traditional Chinese medicine is mainly used for treating the iron-deficiency anemia by methods of tonifying qi, enriching blood, strengthening spleen, tonifying kidney and the like, so that the clinical symptoms of the iron-deficiency anemia are fundamentally improved, the bioavailability of iron can be remarkably improved, and the traditional Chinese medicine has the characteristic of low toxic and side effects. Based on the stimulation of gastrointestinal tract by a single iron preparation and the symptom of slow response of traditional Chinese medicines, the combination of classical blood enriching formulas such as spleen invigorating and hematogenesis formulas and decoction of four ingredients with a small dose of iron preparations has obvious clinical effect.

In view of this situation, the WHO recommends 60mg to 120mg of Iron agent in combination with 400 μ g of folic acid as a daily Iron supplement scheme in Guidelines for the Use of Iron Supplements to invent and Treat Iron deficiency anemia promulgated in 2010 for treating Iron deficiency anemia while reducing the incidence of neural tube malformations. The combination of ferrous iron and folic acid shows that the addition of folic acid can improve the absorption and utilization of iron through long-term experiments in different countries and regions, and the risk of anemia in pre-pregnancy and pregnancy of women in the child-bearing age can be obviously reduced through taking the folic acid-containing iron preparation.

In the treatment process of iron-deficiency anemia, a single iron agent, folic acid, vitamins and the like are added, the main effect is to supplement hematopoietic raw materials, the effect is quick, but gastrointestinal tract injury to a certain degree exists, the situation that the medicine is stopped and the medicine is repeated exists, and the long-term curative effect is poor.

The donkey-hide gelatin is used as a classical eriodictyol medicine for enriching blood, nourishes precious materials and is suitable for long-term administration. In the traditional Chinese medicine theory, women have blood as the basis, anemia belongs to the category of blood deficiency syndrome, women have blood as the basis in physiological activities such as menstruation, pregnancy, parturition, lactation and the like, and donkey-hide gelatin is used as a blood-enriching monarch drug in the application process of doctors of all generations. Sun Simiao on the basis of Beiji Qianjin Yao Fang, specially establishes women's 3 rolls, applies a large amount of formula of donkey-hide gelatin, and mainly takes the effects of sweet nature, enriching blood and nourishing yin, nourishing blood and moistening dryness, and preventing miscarriage. The modern pharmacological research result shows that peptide segments with different molecular masses generated after the hydrolysis of the donkey-hide gelatin can effectively improve the hemoglobin content and the erythrocyte count of a blood-deficiency mouse caused by a bloodletting method, and in a compound blood-deficiency model, the donkey-hide gelatin can obviously increase the endurance, reverse the adverse changes of hematology indexes such as the quantity of erythrocytes and lymphocytes and the like, and obviously reduce the malondialdehyde content in serum, thereby showing that the donkey-hide gelatin has the functions of resisting oxidation, resisting fatigue, strengthening the physique and increasing the physical strength. In the process of modern clinical research, the donkey-hide gelatin is found to increase the thickness of endometrium in ovulation induction and pregnancy assisting cycle, accelerate the growth of endometrium, improve uterine artery blood supply and be beneficial to embryo implantation.

However, no Chinese-western combined composition exists at present, which not only can exert the strong blood-enriching and yin-nourishing efficacy of the donkey-hide gelatin, but also can promote the absorption of the body to iron and folic acid, thereby achieving the effect of treating both principal and secondary aspects of a disease.

Disclosure of Invention

In view of the above, the invention aims to provide a nutritional anemia improving composition and an application thereof, and the nutritional anemia improving composition is based on a concept formula combining traditional Chinese medicine and western medicine, and has a remarkable effect.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a composition for improving alimentary anemia, which is characterized by comprising the following components, by weight, 100-2000 parts of donkey-hide gelatin, 1-20 parts of ferrous fumarate, 0.01-1 part of folic acid, 1-70 parts of cellulose and 2-75 parts of lactose.

Preferably, the donkey-hide gelatin is donkey-hide gelatin powder.

Preferably, the preparation method of the donkey-hide gelatin powder comprises the following steps: concentrating the melted donkey-hide gelatin and then drying in vacuum; the melting steam pressure is 0.05-2.00 MPa, and the melting temperature is 70-100 ℃; the steam pressure of the concentration is 0.12-4.00 MPa, and the temperature of the concentration is 100-135 ℃; the drying temperature is 65-80 ℃, the drying steam pressure is less than 0.09MPa, and the drying vacuum pressure is 0.05-0.07 MPa.

Preferably, the donkey-hide gelatin powder is further sieved after being dried in vacuum; and the sieving is to sieve the donkey-hide gelatin after vacuum drying by a sieve of 60-100 meshes and collect substances below the sieve to obtain the donkey-hide gelatin powder.

The invention also provides a preparation method of the composition, which comprises the following steps: mixing the donkey-hide gelatin, ferrous fumarate, folic acid, microcrystalline cellulose and lactose to obtain a dry mixture; mixing the dry mixture with an ethanol solution, and then performing wet mixing and granulation; and drying the prepared wet granules by air blowing, and sieving to obtain dry granules of the composition.

Preferably, the temperature of the forced air drying is 50-70 ℃.

The invention also provides application of the composition or the dry granules prepared by the preparation method in preparing a medicine for treating nutritional anemia.

Preferably, the dosage form of the medicament comprises: tablet, powder, granule, capsule or pill.

The invention also provides application of the composition or the dry granules prepared by the preparation method in preparing health-care products with auxiliary treatment effect on nutritional anemia.

Preferably, the formulation of the health product comprises: tablet, powder, granule, capsule or pill.

The invention provides a composition for improving alimentary anemia, which is prepared by applying the concept of combination of Chinese and western medicines and taking donkey-hide gelatin, ferrous fumarate and folic acid as main components and adding a proper amount of auxiliary materials. In the embodiment of the invention, the rat model with iron deficiency anemia is respectively treated by using the high concentration, the medium concentration and the low concentration, so that the weight of the rat can be obviously improved, the hemoglobin content is increased, the erythrocyte overstock is improved, and the content of free porphyrinogen is reduced, therefore, the composition can be used for preparing a medicine for treating nutritional anemia or a health-care product for assisting in treating nutritional anemia.

The preparation method of the composition provided by the invention has the processes of mixing, shearing and granulating, is simple and quick in operation, saves working procedures, is wide in application, effectively improves the quality and yield of granules, prepares granules suitable for preparation, and solves the problem of difficulty in preparation forming caused by moisture sensitivity and heat sensitivity of donkey-hide gelatin.

Detailed Description

The invention provides a composition for improving nutritional anemia, which is characterized by comprising the following components in parts by weight: 100-2000 parts of donkey-hide gelatin, 1-20 parts of ferrous fumarate, 0.01-1 part of folic acid, 1-70 parts of cellulose and 2-75 parts of lactose.

The composition comprises donkey-hide gelatin, and the weight portion of the donkey-hide gelatin in the composition is preferably 200-1800 parts, more preferably 300-1200 parts, and most preferably 400-1000 parts. The donkey-hide gelatin is preferably donkey-hide gelatin powder, and the preparation method of the donkey-hide gelatin powder preferably comprises the following steps: concentrating melted colla Corii Asini, and vacuum drying. The melting and the concentration are preferably carried out in a glue melting tank, and the vapor pressure of the melting is preferably 0.05-2.00 MPa, more preferably 1-1.8 MPa, and most preferably 1.5 MPa. The melting is preferably low-temperature melting, the low temperature is preferably 70-100 ℃, more preferably 80-90 ℃, and most preferably 85 ℃. The concentration is preferably high-temperature concentration, and the steam pressure of the concentration is preferably 0.12-4.00 MPa, more preferably 1-3.5 MPa, and most preferably 2.7 MPa. The concentration temperature of the invention is preferably 100-135 ℃, more preferably 110-130 ℃, and most preferably 120 ℃. The drying is preferably vacuum belt drying, and the drying temperature is preferably 65-80 ℃, more preferably 70-76 ℃, and most preferably 72 ℃. The steam pressure of the vacuum drying is preferably less than 0.09MPa, and the pressure of the vacuum drying is preferably 0.05-0.07 MPa. According to the invention, after the donkey-hide gelatin powder is dried in vacuum, sieving is preferably further included; the sieving is preferably to sieve the donkey-hide gelatin after vacuum drying by a sieve of 60-100 meshes, more preferably 70-85 meshes, and most preferably 80 meshes. The invention collects the sieved substances to obtain the donkey-hide gelatin powder. In the present invention, the source of the donkey-hide gelatin is not particularly limited, but is preferably from east donkey-hide gelatin corporation.

The composition comprises ferrous fumarate, and the weight part of the ferrous fumarate in the composition is preferably 2-18 parts, more preferably 5-15 parts, and most preferably 8-12 parts. The ferrous fumarate can be used as a supplement for iron-deficiency anemia, can effectively improve anemia symptoms of pregnant women, children and other people, and has a remarkable curative effect compared with a single iron preparation. In the present invention, the source of the ferrous fumarate is not particularly limited, and any conventional reagent in the art may be used.

The composition comprises folic acid, and the weight portion of the folic acid in the composition is preferably 0.02-0.9 part, more preferably 0.05-0.5 part, and most preferably 0.1-0.4 part. The source of the folic acid is not particularly limited in the present invention, and conventional reagents in the art may be used.

The donkey-hide gelatin can enhance the body constitution of the organism and increase the physical strength, the combination of the ferrous fumarate and the folic acid not only supplements hematopoietic raw materials, but also has the prenatal prevention effect, and the combination of the donkey-hide gelatin, the ferrous fumarate and the folic acid not only can improve the alimentary anemia symptoms, but also can fundamentally reduce the adverse reaction of the gastrointestinal tract after long-term administration, thereby achieving the overall curative effect from inside to outside, simultaneously promoting the absorption of the organism to the iron and the folic acid and achieving the effect of treating both principal and secondary aspects of a disease.

Cellulose is included in the compositions of the present invention, preferably microcrystalline cellulose. The weight part of the cellulose in the composition is preferably 5-60 parts, more preferably 10-50 parts, and most preferably 25-45 parts. The microcrystalline cellulose has good adhesion and disintegration, particularly overcomes the influence of starch, dextrin and the like on heat, water and main content measurement in the preparation of wet granules, and is an excellent filling agent. The source of the cellulose in the present invention is not particularly limited, and conventional reagents in the art may be used.

The composition comprises lactose, and the weight part of the lactose in the composition is preferably 5-70 parts, more preferably 10-55 parts, and most preferably 25-48 parts. The lactose has good fluidity, can effectively improve the viscosity of the donkey-hide gelatin in a formula, and improves the preparation process formability. The source of the lactose is not particularly limited in the present invention, and conventional reagents in the art may be used. In the invention, the microcrystalline cellulose and the lactose are prepared by a process according to a proper proportion, so that the viscosity of the donkey-hide gelatin can be effectively improved in operation and enlarged production, and the practical application is facilitated.

The invention also provides a preparation method of the composition, which comprises the following steps: mixing the donkey-hide gelatin, ferrous fumarate, folic acid, microcrystalline cellulose and lactose to obtain a dry mixture; mixing the dry mixture with an ethanol solution, and then performing wet mixing and granulation; and drying the prepared wet granules by air blowing, and sieving to obtain dry granules of the composition. The donkey-hide gelatin, the ferrous fumarate, the folic acid, the microcrystalline cellulose and the lactose are preferably mixed in a granulation pot, the mixing is preferably dry-mixed by adopting a stirring paddle and a cutting knife, and the rotation speed of the stirring paddle is preferably 8-10 Hz; the rotating speed of the cutting knife is preferably 5-10 Hz. The ethanol solution is preferably 95% ethanol, and when the ethanol solution is mixed with the ethanol, the rotating speeds of a stirring paddle and a cutting knife are preferably kept unchanged during dry mixing. The invention adjusts the rotating speed of the stirring paddle and the cutting knife after adding the ethanol, and carries out wet mixing and granulation. The rotating speed of the stirring paddle after adjustment is preferably 10-15 Hz; the rotating speed of the cutting knife is preferably 8-10 Hz. The wet granules obtained are dried by blowing at 60 ℃ for standby. The dried coarse particles were placed on a shaker screen and shaken for 5min, the mass of the coarse particles retained on each screen was recorded, and the coarse particles were classified into 3 grades, clumps, granules and fines. The part which can not pass through the No. 1 sieve is called agglomerate; the section between screens No. 2 and No. 5 is called a pellet; the remainder is called fines. The temperature of the air-blast drying is preferably 50-70 ℃, more preferably 55-65 ℃, and most preferably 60 ℃. The water content of the dry particles of the composition prepared by the invention is preferably 3-5%, more preferably 3.2-4%, and most preferably 3.5%. The particle size of the dry particles of the composition prepared by the invention is preferably 180-350 mm.

The invention also provides application of the composition or the dry granules of the composition prepared by the preparation method in preparing a medicine for treating nutritional anemia. The dosage form of the medicament of the present invention preferably comprises: tablet, powder, granule, capsule or pill. The preparation method of each dosage form of the medicament is not particularly limited, and the conventional method in the field can be utilized.

The invention also provides application of the composition or the dry granules of the composition prepared by the preparation method in preparing health-care products with auxiliary treatment effect on nutritional anemia. The formulation of the health care product comprises: tablet, powder, granule, capsule or pill. The preparation method of each dosage form of the health care product is not particularly limited, and the conventional method in the field can be utilized.

The nutritional anemia improving composition and the use thereof provided by the present invention will be described in detail with reference to the following examples, but they should not be construed as limiting the scope of the present invention.

Example 1

Melting colla Corii Asini at 85 deg.C under 1.5MPa of steam pressure, and concentrating the melted colla Corii Asini at 120 deg.C under 2.7MPa in a gelatin melting tank with opening degree of less than 60; drying concentrated colla Corii Asini by vacuum belt type to obtain powder, sieving with 80 mesh vibrating sieve at 78 deg.C under steam pressure of 0.09MPa and vacuum pressure of 0.06MPa, and removing oversize product to obtain colla Corii Asini powder.

Example 2

500g of the donkey-hide gelatin powder prepared in example 1, 11g of ferrous fumarate, 0.1g of folic acid, 30g of microcrystalline cellulose and 32g of lactose were added to a mixer, a paddle and a cutter were started to conduct dry mixing for 1min at a paddle rotation speed of 8Hz and a cutter rotation speed of 5Hz, 90% ethanol was added, wet mixing was conducted for 1min at a paddle rotation speed of 10Hz and a cutter rotation speed of 8Hz, and wet mixing and granulation were conducted. The prepared wet granules were air-dried at 60 ℃ for 15 min. The prepared dry particles are placed in a granulator, and lump masses are sieved out until the particle size of the obtained particles is uniformly distributed and contains a proper amount of fine powder.

Example 3

500g of the donkey-hide gelatin powder prepared in example 1, 10g of ferrous fumarate, 0.2g of folic acid, 40g of microcrystalline cellulose and 42g of lactose were added to a mixer by weight, and a paddle and a cutter were started to conduct dry mixing for 1min at a paddle rotation speed of 10Hz and a cutter rotation speed of 8Hz, and 95% ethanol was added thereto for wet mixing for 1min at a paddle rotation speed of 12Hz and a cutter rotation speed of 9Hz, to conduct wet mixing and granulation. The obtained wet granules were air-dried at 60 deg.C for 20 min. The prepared dry particles are placed in a granulator, and lump masses are sieved out until the particle size of the obtained particles is uniformly distributed and contains a proper amount of fine powder.

Example 4

600g of the donkey-hide gelatin powder prepared in example 1, 11g of ferrous fumarate, 0.1g of folic acid, 42g of microcrystalline cellulose and 45g of lactose were added to a mixer, a paddle and a cutter were started to conduct dry mixing for 1min at a paddle rotation speed of 8Hz and a cutter rotation speed of 10Hz, 95% ethanol was added, wet mixing was conducted for 1min at a paddle rotation speed of 15Hz and a cutter rotation speed of 10Hz, and wet mixing and granulation were conducted. The prepared wet granules were air-dried at 60 ℃ for 25 min. The prepared dry particles are placed in a granulator, and lump masses are sieved out until the particle size of the obtained particles is uniformly distributed and contains a proper amount of fine powder.

Experiments were carried out using the granular compositions prepared in examples 2 to 4 according to the evaluation and test method for improving nutritional anemia in "health food test and evaluation technical Specification":

1. establishing iron deficiency anemia rat model

100 healthy weaning clean SD male rats (with the body weight of 40-50 g) are selected, are fed with low-iron feed and deionized water after being adapted for 4 days in an experimental environment, a stainless steel cage and a feeding tank are adopted, and all rats are subjected to tail blood collection for Hb measurement after 2 weeks.

2. Effect of the compositions of the invention on rat body weight

70 rats with Hb less than 100g/L are selected as experimental animals, and are randomly divided into a low-iron control group and 6 experimental groups according to Hb level and body weight of anemic rats, 10 rats are each group, each group is continuously fed with low-iron feed, the experimental groups are respectively fed with test samples with different doses, and the experimental groups are respectively fed with low (174mg/kg BW), medium (522mg/kg BW) and high (870mg/kg BW) test samples. All experimental animals were orally administered the test substance and distilled water in a gavage volume of 10mL/kg BW for 30 consecutive days. The low iron control group was dosed with equal amounts of distilled water and weighed weekly, with the results shown in table 1:

table 1 effect of tablet on rat body weight (n ═ 10, x ± s, g)

After the test, the weight of rats in each dose group of 3 formula samples is larger than that of a model control group, the average weight of the rats after the test is 1.10-1.43 times that of the control group, and the difference has statistical significance (P is less than 0.05).

3. Effect of the compositions of the invention on rat hemoglobin

Taking rat tail blood with 10 μ L quantitative capillary, placing into plastic tube containing 2.5mL potassium ferricyanide reagent, oscillating sufficiently, standing in dark place for 15min, measuring at wavelength of 540nm, and measuring hemoglobin standard and reference standard substance.

The results of hemoglobin measurement in each group of rats 30 days after oral administration of the tablets are shown in Table 2:

TABLE 2 Effect of the compositions of the present invention on rat hemoglobin

The hemoglobin of the rats in the low, medium and high dose groups is higher than that of the control group in the anemia model, the average hemoglobin increase is 52.2 +/-6.5 mu g/L after 30 days, the increase is about 90 mu g/L compared with that of the control group, the increment is obvious, and the comparative difference between the groups has statistical significance (P is less than 0.05).

4. The effect of the composition of the present invention on rat hematocrit and free protoporphyrin in erythrocytes was achieved by aspirating 500. mu.L of whole blood, injecting into a hematocrit tube, and measuring hematocrit with a Yapei hemanalyzer according to the hematology analyzer method, with the experimental results shown in Table 3.

Adding 0.02mL of heparin anticoagulated whole blood into 0.15mL of diatomite suspension and 4.0mL of acetic acid-ethyl acetate mixed solution, oscillating for 2-3 min, centrifuging at 3000r/min, extracting supernate with 0.5M HCl solution, performing fluorescence measurement (excitation wavelength is 403nm, emission wavelength is 605nm) on a fluorescence spectrophotometer, and calculating an FEP value according to fluorescence intensity. The results of the experiment are shown in table 3.

TABLE 3 Effect of the compositions of the invention on rat erythrocyte hematocrit and free protoporphyrin in the erythrocytes

Group of	Erythrocyte pressure (%)	P value	Free porphyrinogen (ug/L)	P value
					Control group of anemia model	33.8±2.4	/	980.7±51.4	/
Low dose group	82.2±4.6	0.000	314.5±33.7	0.000
					Middle dose group	84.4±22	0.000	330.2±18.6	0.000
High dose group	85.7±3.1	0.000	393.3±39.0	0.000

After the test, the volume of the erythrocyte in each dose group of the formula sample is averagely higher than that in the model control group by 50.3 +/-0.9%, and the difference has statistical significance (P is less than 0.05). The content of free protoporphyrin in the red blood cells of each experimental dose group is 643.7 +/-21 mu g/L lower than that of an anemia model control group, and the comparative difference between the groups has statistical significance (P is less than 0.05).

The invention provides a composition for improving nutritional anemia, which can obviously increase the body weight of an anemic rat model, increase the hemoglobin content, improve the red blood cell overstock and reduce the content of free porphyrinogen, and can be used for preparing a medicine or a health-care product for improving nutritional anemia.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. The composition for improving nutritional anemia is characterized by comprising the following components in parts by weight: 100-2000 parts of donkey-hide gelatin, 1-20 parts of ferrous fumarate, 0.01-1 part of folic acid, 1-70 parts of cellulose and 2-75 parts of lactose;

the colla corii asini is colla corii asini powder;

the preparation method of the donkey-hide gelatin powder comprises the following steps: concentrating the melted donkey-hide gelatin and then drying in vacuum; the melting steam pressure is 0.05-2.00 MPa, and the melting temperature is 70-100 ℃; the steam pressure of the concentration is 0.12-4.00 MPa, and the temperature of the concentration is 100-135 ℃; the temperature of the vacuum drying is 65-80 ℃, the steam pressure of the vacuum drying is less than 0.09MPa, and the pressure of the vacuum drying is 0.05-0.07 MPa;

sieving the donkey-hide gelatin powder after vacuum drying; and the sieving is to sieve the donkey-hide gelatin after vacuum drying by a sieve of 60-100 meshes and collect substances below the sieve to obtain the donkey-hide gelatin powder.

2. A method of preparing the composition of claim 1, comprising the steps of: mixing the donkey-hide gelatin, ferrous fumarate, folic acid, microcrystalline cellulose and lactose to obtain a dry mixture; mixing the dry mixture with an ethanol solution, and then performing wet mixing and granulation; and drying the prepared wet granules by air blowing, and sieving to obtain dry granules of the composition.

3. The method according to claim 2, wherein the temperature of the forced air drying is 50 to 70 ℃.

4. Use of the composition of claim 1 or dry granules prepared by the preparation method of claim 2 or 3 for preparing a medicament for treating nutritional anemia.

5. The use of claim 4, wherein the medicament is in a dosage form comprising: tablet, powder, granule, capsule or pill.

6. Use of the composition of claim 1 or the dry granules of the composition prepared by the preparation method of claim 2 or 3 in the preparation of health products for the adjuvant treatment of nutritional anemia.

7. The use of claim 6, wherein the formulation of the nutraceutical comprises: tablet, powder, granule, capsule or pill.