WO2022157745A1

WO2022157745A1 - Multi micro-nutrient (mmn): composition for pregnancy

Info

Publication number: WO2022157745A1
Application number: PCT/IB2022/050634
Authority: WO
Inventors: Sameer Agarwal; Surbhi Gupta
Original assignee: Sameer Agarwal; Surbhi Gupta
Priority date: 2021-01-25
Filing date: 2022-01-25
Publication date: 2022-07-28

Abstract

The present invention provides a formulation of multi micronutrient (MMN) of 3 -stage course for each trimester of pregnancy comprising: vitamins and minerals for first trimester of pregnancy; vitamins and minerals for second trimester of pregnancy; and vitamins and minerals for third trimester of pregnancy. The present invention furthermore provides a kit having a formulation of multi micronutrient (MMN) of 3 -stage course for each trimester of pregnancy.

Description

MULTI MICRO-NUTRIENT (MMN); COMPOSITION FOR PREGNANCY

FIELD OF INVENTION

The present invention relates to a novel Multi Micro -nutrient (MMN) formulation and trimester- wise system for pregnant women, especially, women in India.

BACKGROUND OF THE INVENTION

Pregnancy places a high demand in terms of physiological needs of women. Nutritional intake during pregnancy not only determines growth and development of the fetus but also impacts the health of that child in his or her lifetime. In the baby, micronutrient deficiency during pregnancy, can lead to megaloblastosis, neural tube defects, placental and foetal defects, low birth weight and premature delivery. It has also been found that nutritional intake during pregnancy defines the mother’s well-being while she is pregnant as well as postdelivery. Nutritional deficiencies can cause various pregnancy symptoms such as gestational diabetes, preeclampsia, thyroid, leg cramps, insomnia, nausea, post-natal depression etc.; and can also lead to long-term issues in the mother such as osteoporosis, hypertension and diabetes.

On anaverage 20% to 30% of pregnant women suffer from a micronutrient deficiency without prophylaxis and about 75% would show a deficit of at least 2-3 micronutrients.

Vitamins and Minerals, together categorised as multi micronutrients, are commonly administered during pregnancy. The purpose is firstly, to treat micronutrient deficiencies in the pregnant woman; and secondly, to meet the increasing physiological demands by filling the gaps in her diet.

The role of the micronutrients in pregnancy is well established. Let’s take the case of Vitamin B complex, composed of eight B vitamins- vitamins Bi (thiamine), B2 (riboflavin), B3 (niacin), Be (pyridoxine) and B12 (cyanocobalamin), which are water-soluble vitamins required for the production and release of energy in cells and for the metabolism of macronutrients. These vitamins act as coenzymes in a number of enzyme-dependent cellular intermediary metabolic pathways for energy generation and blood cell formation. Vitamin B12 and folate convert homocysteine to methionine that is essential for the methylation of DNA, RNA, proteins, neurotransmitters and phospholipids and deficiency in these vitamins can affect cellular growth and nerve tissue development. Studies have indicated that despite vitamin supplementation, deficiency of vitamin A, B6, niacin and thiamine may occur during all trimesters. B12 deficits increase during the second and third trimesters indicating that as pregnancy progresses the B12 demand by the foetus may be heightened.

Similarly, folate is a water-soluble B vitamin present in leafy green vegetables, yeast extract and citrus fruits such as oranges. Folic acid is most crucial in pregnancy from preconception until at least 12 weeks. Supplementation of folic acid during preconception and early pregnancy is critical and can prevent 40-80% of neural tube defects (NTDs) such as spina bifida. However, the dietary folic acid is converted to acid to L- methylfolate in the body through a number of enzymatic reactions and lastly using enzyme methyl-tetrahydrofolate reductase (MTHFR) before it can be absorbed by the body. It has been reported that about 40% to 60% of the population has genetic polymorphisms in the MTHFR gene and therefore are unable to convert supplemental folic acid to its active form, L- methylfolate. This can lead to pregnancy complications such as miscarriage, preeclampsia and birth defect. In fact, 80% women in India are folate deficient. Based on the available data of high prevalence of the genetic polymorphisms in MTHFR enzyme, using L-methly folate supplementation can help reduce blood folate deficiencies

Iron is another important micro -nutrient which is involved in number of important cellular processes. Iron is involved in synthesis of haemoglobin and myoglobin, including oxygen transport, respiration, growth, gene regulation, and the proper functioning of iron-dependent enzymes. Anaemia has been estimated to affect 40% of pregnant women globally, with the highest prevalence in the regions of South-east Asia (49%), and nearly 70% Indian woman are said to be anaemic. It is important to treat anaemia with haematopoietic nutrients which include Iron along with Vitamin C, Folate and Vitamin B12.

Clearly, the nutritional requirement of an expectant mother changes depending on the different geographical regions and the traditional food preference prevalent in a particular region. The diet of an average Indian, both in urban & rural sector, is known to be rich in carbohydrates but micronutrient deficient. It has been reported that one in two pregnant women intakes micronutrients below estimated average requirement. Therefore, micronutrient supplementation during pregnancy is suggested by doctors. However, the formulations currently available are not nutritionally adequate to make up for the all deficiencies in the diet of an Indian expectant mother. Besides there is no product that can effectively provide the essential micronutrients in a one-stop system, forcing the doctors to prescribe many no. of micronutrient tablets separately (such as, folic acid, Iron, Calcium, Vitamin D, B-complex etc.). The increase in number of tablets is known to affect patient compliance. Infact, studies show that 40% patients show poor adherence to therapy when multiple pills are prescribed.

Apart from this, while an average Indian pregnant woman ends up taking 3-4 tablets/day, she continues to suffer from pregnancy induced symptoms like morning sickness, cramps, Urinary Tract Infection, diabetes, hypertension etc.; thereby, requiring further medication to resolve them. Too many medicines have their own side-effects such as bloating, burping, constipation etc. In essence, in spite of so many medications the 9-month journey of the pregnant mother is full of physiological discomfort and yet does not ensure her and the child’s wellbeing.

Keeping the above in view, there is a need to provide a comprehensive, multi Micronutrients (MMN) formulation that effectively provides all the essential multi micronutrients to the mother, ensuring her immediate and long-range wellbeing as well as the same for the child; and all the above to be provided in a simple one-stop package which ensures easy adherence to therapy.

European Patent No. 0662825B1 provides various multi micronutrients to pregnant women in a trimester-wise administered formulation. Despite the effort taken to provide unique formulation for each trimester, it does not include nutritional elements which reduce pregnancy induced symptoms such as, morning sickness, leg-cramps, gestational diabetes, pre-eclampsia, gestational thyroid, constipation and gastro-intestinal side-effects, which are commonly experienced by most women during pregnancy. Thus, the prenatal supplementation remains incomplete in terms of providing a trimester-wise solution which is good for both mother and the baby. Secondly, it is recognized that various groups of human population need different types and quantities of micronutrients - based on their diet, genetics and commonly found deficiencies. The above patent caters to the need of European population and does not address the needs of the Indian population. Thirdly, it overlooks the benefits of various important antioxidants such as Selenium and Manganese; trace minerals like Molybdenum, Boron, Chromium; and other nutrients like Vitamin K, Omega etc. - all, which play a vital role in foetal brain and organ development, cognitive benefits, reducing the chances of birth defects and improving maternal health.

It would be therefore desirable to provide a multi-micronutrient supplementation which overcomes the deficiencies of the prior art.

DETAILED DESCRIPTION

The present invention overcomes the shortcomings of the prior art and provides a unique system and kit for nutritional supplementation to a pregnant woman, which comprises: a) a first composition comprising the following ingredients for the first trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron; Omega; and Anti-emetic anti-nausea blend; (Optionally, Iron, Calcium, Choline, Inositol, Pre and Probiotics, and Amino acids) b) a second composition comprising the following ingredients for the second trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron, Iron, Calcium; Omega; (Optionally, Choline, Inositol, Amino acids, Pre and Probiotics) c) a third composition comprising the following ingredients for the third trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron, Iron, Calcium; Omega; and Bowel Regulator for constipation; (Optionally, Choline, Inositol, Amino acids, Pre and Probiotics, and Urinary Tract Infection blend)

In particular, the composition useful as nutritional supplement in the first trimester comprises a combination of: Vitamin A- 600-6000mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to lOOmg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2-10 mg, preferably lOmg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg;

Vitamin B9- 0.2 to lOmg, preferably 5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg;

Zinc - 10-40mg preferably 12mg;

Iodine - 100-300pg, preferably 200pg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 206mg;

Omega3- 50-2000mg, preferably lOOmg;

Anti-emetic anti-nausea blend- 50mg-600mg, preferably 200mg;

Further, the composition useful as nutritional supplement in the second trimester comprises a combination of:

Vitamin A- 600-6000mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to 100 mg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2 -10 mg, preferably 3 mg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg; Vitamin B9- 0.2 to lOmg, preferably 0.5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg;

Iodine - 100-300pg, preferably 200pg;

Zinc - 10-40mg preferably 12mg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 206mg;

Iron - 30-100 mg, preferably 60mg;

Calcium - 300-800 mg, preferably 500mg;

Omega 3- 50-2000mg, preferably 200mg;

Additionally, the composition useful as nutritional supplement in the third trimester comprises a combination of:

Vitamin A- 600-6000mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to 100 mg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2 -10 mg, preferably 3 mg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg;

Vitamin B9- 0.2 to lOmg, preferably 0.5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg; Iodine - 100-300pg, preferably 200pg;

Zinc - 10-40mg preferably 12mg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 310mg;

Iron - 30-100 mg, preferably 60mg;

Calcium - 300-800 mg, preferably 500mg;

Omega 3- 50-2000mg, preferably 200mg;

Digestive blend- 50mg-600mg, preferably 200mg

The inventors after much study and research have found that the above unique combination of vitamins and minerals together with other supplements is useful in nourishing and maintaining the nutritional balance in a pregnant woman. It is notable that in each of the trimesters, the amount of vitamins and minerals is varied to meet the needs of the body, growing foetus, and manage the typical pregnancy symptoms of that trimester. The units of the vitamins and amount thereof is the result of careful and purposeful selection.

Vitamin A:

Vitamin A is also an important element to be consumed for visual health, immune function and fetal growth and development. It is a known fact that most Indian women are deficient in Vitamin A. Vitamin A deficiency can cause visual impairment in the form of night blindness and may increase the risk of illness and death from childhood infections such as measles and diarrhea. The effects are seen much after the child is born. It is important for maintenance of mother’s eye health. Vitamin A along with Vitamins C and E, Manganese and Selenium act as antioxidants which prevents oxidative stress in mother during pregnancy. This reduces chances of foetal complications. Since high dose of Vitamin A is teratogenic, only 25% of the required dose is used for the supplement - the rest is consumed via a typical healthy diet. Vitamin A in the composition is present in as mixture of retinol and beta carotene. Vitamin A is at its highest during the third trimester of pregnancy due to accelerated fetal development and the physiological increase in blood volume during this period. Therefore, keeping all these factors in mind, the composition provides 600 -6,000 pg preferably 1600 pg during the entire course of pregnancy.

Vitamin B:

One of the most important vitamins to be taken during pregnancy is vitamin B often called vitamin B complex. It isa very important aspect of a mother’s nutrition during pregnancy, especially vitamins B6, B9, and B12. These three specifically help minimize the risk of birth defects as well as relieve some symptoms of pregnancy.

Vitamin B complex (as is popularly known is a mixture of Vitamin Bl, B2 and B3) acts as coenzymes in several intermediary metabolic cellular pathways particularly for energy generation and blood cell formation. Therefore, vitamin B complex is required for release of energy in cells and also for the metabolism of protein, fat and carbohydrates. Vitamin B 12 functions with folate is essential for the methylation of DNA, RNA, proteins, neurotransmitters and phospholipids. Deficiency in these vitamins can therefore impact on cellular growth as well as on nerve tissue development. Vitamin B complex is essential for baby’s brain and spine; each of the vitamins help each other synergistically in the production of energy. Vitamin B complex along with copper helps in maternal and foetal brain development. The main source of vitamin B complex is animal product, nuts and vegetables. However, in a primarily vegetarian diet proper amount of vitamins are not available due to poor soil quality. Hence, to complete the required quantity, supplementation is required.

B-l (Thiamine): Supports baby’s healthy brain development. In the first trimester, the composition provides 1.6 mg, though it may be taken between 2-8mg. Since it is very important for the brain development, it is maintained constant throughout the pregnancy. It improves mother’s energy, mood and stress levels by aiding metabolism. In the baby it provides energy to the brain, helps in the formation of Red Blood Cells. It may be present in the range of 0.2 to 100 mg, preferably 1.6mg

B-2 (Riboflavin): Keeps eyes healthy and skin glowing. In the first trimester, it is ideal to administer 0.2 to 100 mg; the composition provides 2mg, which is determined as ideal for proper skin development. It is maintained constant throughout the pregnancy. B-3 (Niacin): It is important as it metabolizes carbohydrate to produce energy, helps in functioning of Central Nervous System, digestive system, skin health. In the first trimester, it is ideal to administer 2 to 35 mg; the composition provides 18 mg, it is maintained constant throughout the pregnancy.

B-5 (Pantothenic Acid): Reduces leg cramps and helps produce essential pregnancy hormones. In the first trimester, it is ideal to administer 1-10 mg; the composition provides 5mg, which is determined as ideal for proper skin development. It is maintained constant throughout the pregnancy.

B-6 (Pyridoxine): Aids the development of baby’s nervous system and brain. In the first trimester it is found to prevent vomiting and nausea. It also provides energy to the mother. In the fetus, it helps in formation of red blood cells and balances homocysteine levels. In the first trimester, it is ideal to administer 8-15 mg; the composition provides lOmg. In second and third trimester, it is ideal to administer 2 to 10 mg the composition provides 3 mg.

B-7 (Biotin): Deficiency is often caused by pregnancy, so increased consumption is vital. In the first trimester, it helps with embryogenesis. It also helps in maintaining the hair and skin of the mother. It works synergistically with other B -vitamins in the production of energy. It is ideal to administer 10 pg - 10 mg; the composition provides 30 pg, which is determined as ideal for proper development of the fetus. It is maintained constant throughout the pregnancy at about 30 pg.

B-9 (Folic Acid): Plays a vital role in reducing the risk of birth defects. In the first trimester, it supplements and eliminates deficiency, helps in prevention of neural tube defects. It also helps mother prevent anaemia and peripheral neuropathy. In the foetus it prevents congenital abnormalities. Vitamin B2, C and D along with Folate helps in better prevention of neural tube defects. Vitamin B9 is in the form of L-Methylfolate which is 7 times higher bioavailable then folic acid. Since most Indian females are folate deficient therefore supplementation of 5mg dietary folate is required in the first trimester. Thereafter, in second and third trimesters, for maintaining levels of folate 0.5mg dietary folate is sufficient.

B-12 (Cobalamin): It maintains and supports the development of mother and baby’s nervous system. It also prevents Low Birth weight and controls foetal brain development. In the first trimester, it is ideal to administer 0.25 - 1500 pg; the composition provides 3.6pg, which is determined as ideal for proper development of the fetus as well as provide energy and blood flow to the mother.

Vitamin C:

Vitamin C is a water-soluble vitamin and powerful antioxidant which is essential as it a well- known immunity booster. It also plays an important role in the development of the foetus and reduces the risk of developing cardiovascular disease and certain cancers. It is important for tissue repair and wound healing, helps in development of child’s bones and teeth. Vitamin C also aids in the body’s production of collagen. Vitamin A along with Vitamins C and E, Manganese and Selenium act as antioxidants which prevent oxidative stress in mother during pregnancy. Thereby, reducing chances of foetal complications. Vitamin C when combined with Iron, improves its absorption. As per the invented composition, the amount may be 30- 200mg, preferably 60mg for each trimester.

Vitamin D:

Vitamin D deficiency (VDD) is a common problem in reproductive-aged women and has become a major public health problem worldwide. The effect of VDD in pregnancy has been associated with several adverse pregnancy outcomes. Lack of vitamin D or insufficient amount of vitamin D can not only result in poor bones for the children but also affect the children throughout their life. Such children are prone to osteoporosis. It improves calcium absorption and supports bone health of both mother and foetus. 400 IU is ideal maintenance doze for a pregnant woman. It can slowly build her Vitamin D reserve without causing any side-effects. If a certain woman is found deficient in Vitamin D, then she can be supplemented separately for a couple of weeks. In view of these factors, the composition of the invention employs vitamin D in an amount of 200-4000IU preferably 400 IU in each trimester.

Vitamin E:

Vitamin E is necessary for reproduction. It is a powerful lipid-soluble antioxidant. Vitamin E helps your body create and maintain red blood cells, healthy skin, eyes and strengthens the natural immune system. Vitamin E helps to reduce the risk of pregnancy complications involving oxidative stress, such as pre-eclampsia. Boosts antioxidant defence and protects cell membrane. Enhances immune function. Helps clot formation in blood. Vitamin E works along with vitamin A, C, selenium and manganese as anti-oxidants. Keeping in view these objectives, the composition of the invention employs Vitamin E in an amount of 7-400mg preferably lOmg during each trimester.

Vitamin K:

Vitamin K plays an important role in blood clotting, healthy bone development and protein formation in the liver. It is particularly important during labour. Vitamin K deficiency can lead to a haemorrhagic disease that increases the risk of child bleeding too much. It is essential for bone health, provides immune support to the mother and promotes healthy muscle function; protein formation in the liver. Vitamin K along with Vitamin D works together for calcium absorption bone development. During the third Trimester, it prevents excess blood loss during delivery. Keeping in view these objectives, the composition of the invention employs Vitamin K in an amount of 25-90mcg preferably, 55pg during each trimester.

Zinc:

Zinc has a major role to play in body development and functioning of the mother and her foetus. Zinc can be naturally found in certain food items or consumed in the form of supplements. Zinc must be taken in its elemental form and not in form of any salt. It increases immunity when taken along with Vitamin C. It helps in the production of haemoglobin and also prevents preterm birth. It also helps in proper absorption of Vitamin A and Iron. Most Indians are zinc deficient due to agricultural deprivation of the nutrient. Maternal deprivation also leads to anaemic children. Therefore, Zinc supplementation is crucial in pregnancy. Zinc requirements during pregnancy is between 5-40 mg. In addition to the zinc accrued by the foetus, zinc is deposited in the placenta, amniotic fluid, and uterine and mammary tissue, hence the composition provides 12mg for each of the trimesters.

Copper:

Copper plays an important role in electron transport, neurotransmitter synthesis, collagen cross-linkage, and melatonin production and is an important factor in the coagulation cascade. Copper is absorbed by the proximal small intestines and transported to the liver. Toxicity associated with abnormal metabolism, as seen in Wilson’s disease, can result in excessive copper accumulation and deposition in many tissues. This can lead to cardiac dysfunction, liver cirrhosis, pancreatic dysfunction and neurological abnormalities. During pregnancy also, trace amounts of copper is needed. Copper is essential for red blood cell formation, it helps form baby's heart, blood vessels, skeletal and nervous systems. It helps in production of melanin. Copper works with Iron in maintaining haemoglobin levels. Deficiency of copper leads to teratogenicity. Supplementation of copper helps the transportation of iron in the body. Keeping in view these objectives, the composition of the invention employs copper in an amount of l-2mg, preferably 1.7 mg during each trimester.

Selenium:

Selenium is fat-soluble, but is very important for protecting the body from damage caused by free radicals and infections. This vital antioxidant helps regulate the immune system and thyroid function. Selenium is also essential for reproduction, and DNA production. It acts as an antioxidant; regulates immune response; and helps in functioning of Thyroid Hormone. It along with Vitamin A, C and E acts as anti-oxidant. Also, along with iodine helps in thyroid function. Keeping in view these objectives, the composition of the invention employs selenium in an amount of 30-70mcg, preferably 40mcg during each trimester.

Manganese:

Manganese is an important mineral because it helps the growing foetus to form bone and cartilage. It acts as an antioxidant and prevents cell damage of both mother and foetus. Also helps in formation of bone and cartilage. It maintains overall energy level in the mother. Manganese along with Selenium, vitamin A, C and E act as an antioxidant and reduces oxidative stress. Supplementing Selenium and Manganese have long-range benefits, they protect babies from developing high blood pressure in their later years. Keeping in view these objectives, the composition of the invention employs manganese in an amount of 2-5 mg, preferably 4mg during each trimester.

Chromium:

Chromium is important for the developing foetus as it helps with protein building in the tissues of the foetus. It plays an important role in the breakdown of lipids, carbohydrate, and protein. It stimulates fatty acid and cholesterol synthesis; they are important for brain function and other body processes. Therefore, chromium is an essential trace nutrient required during pregnancy for the health and well-being of both the mother and the developing foetus. Chromium along with Vitamin D helps in prevention of gestational diabetes. During pregnancy chromium becomes deficient putting pregnant female at risk of developing gestational diabetes. Keeping in view these objectives, the composition of the invention employs manganese in an amount of 20-100mcg, preferably 50 mcg during each trimester.

Magnesium:

Magnesium (Mg) is a very important and essential mineral which is required by human body in substantially large amounts. It works with many enzymes to regulate body temperature, aids in synthesis nucleic acids, and proteins as well as maintaining electrical potentials in nerves and muscle membranes. It also has an important role in modulating vasomotor tone and cardiac excitability. Mg is sourced from dairy products, breads and cereals, legumes, vegetables, and meats etc. Processing of foods can lead to high depletion of Mg. During pregnancy, there is a greater need for magnesium than in a normal human. Magnesium deficiency can lead to many important complications during pregnancy including gestational diabetes mellitus [GDM], pregnancy-induced hypertension [HTN], leg cramps, and preeclampsia. It is also associated with low birth weight of the child, intrauterine growth retardation [IUGR], and preterm birth. Magnesium helps to resolve leg-cramps, has a calming effect on the mother’s mind and benefits her sleep - commonly found issues in the third trimester. Therefore, the composition of the invention as used in the first and second trimester contains 150- 300 mg magnesium, preferably 206 mg; while in the third trimester, the amount may be between 200-400 mg, preferably 306 mg.

Molybdenum;

Molybdenum works in the body to break down proteins and other substances. Mineral involved in the functioning of several important enzymes in the body. It aids in carbohydrate and fat metabolism and helps in iron utilization. It contributes to normal sulphur amino acid metabolism. Vegetables and various animal products and fruits are low in molybdenum. Therefore, supplementation is required to fulfil the deficiency. Keeping in view these objectives, the composition of the invention employs molybdenum in an amount of 45 mcg during each trimester. Iron:

Iron is important as it helps the body to produce more blood. During pregnancy, the blood volume doubles. In India, most women are iron deficient. An average pregnant woman needs about 30 mg of elemental iron per day to meet the new demands of extra blood volume, the developing placenta, and growing fetus. Having low blood volume can lead to complications during delivery and the postpartum period. Iron along with Vitamin B 12, Folate and magnesium helps in improving anemia. Vitamin C helps in better absorption of iron in the body. Keeping in view these objectives, the composition of the invention employs elemental iron from the second trimester in an amount of 12-100mg, preferably 60mg per day dose. Further, the iron which is added in the composition is Time- Released, that is, it is released slowly in timed and sustained manner so that it is better absorbed and the woman does not suffer from constipation and black stools - which is a common side effect of high-dose iron supplementation.

Calcium:

Calcium is important in building teeth and bones, calcium also keeps blood and muscles moving and helps your nerves send messages from the brain to the rest of the body. During pregnancy, in case the mother is deficient in calcium the body will utilise the calcium of the mother’s bones to ensure that the bones and teeth of the foetus are well developed. It is for this reason that pregnant women are often recommended to take calcium supplements. Calcium and magnesium help in maintaining blood pressure and therefore prevent hypertension and pre-eclampsia during pregnancy. Keeping in view these objectives, the composition of the invention employs elemental calcium from the second trimester, in an amount of 500-1200mg preferably 500mg per day dose. By ensuring such amount in the composition, the overall health of the pregnant women as well as their future wellbeing is ensured as these women would not suffer from osteoporosis or such conditions in their later years.

Boron:

Boron is as important as other elements. It can kill yeast that cause vaginal infections. It also has antioxidant effects. Boron is needed for optimal calcium metabolism, prevents bone loss. Keeping in view these objectives, the composition of the invention employs Boron in an amount of 100 mcg to lOmg preferably, 150 mcg. Iodine:

During pregnancy, there is a high demand for iodine during pregnancy. During the first trimester, thyroid hormones for embryonic and foetal tissues rely exclusively on the available maternal hormones; hence, iodine deficiency in the mother may have a negative impact on prenatal development. Clinical studies have reported a relationship of iodine deficiency and maternal hypothyroxinaemia during pregnancy with impaired neurocognitive and psychological development of the children. To cater to these needs the composition of the invention employs iodine between 100-300 pg, preferably 200 pg in all trimesters.

Omega:

Omega is important during pregnancy as they are critical building blocks of foetal brain and retina. Omega fatty acids may also play a role in determining the length of gestation and in preventing perinatal depression. Omega fatty acids has been shown to prevent pre-term labour and delivery, lower the risk of preeclampsia, and may increase birth weight. Omega deficiency also increases the mother's risk of post-natal depression. Keeping in view these objectives, the composition of the invention may haveOmega 3 (EPA and DHA in a ratio of 2:3) in an amount 50-1000mg, preferably lOOmg in first trimester, and 200mg in second and third trimester. It may also have Omega 6 and Omega 9 in an amount from 50-500 mg.

Anti-emetic Anti-Nausea blend:

Anti-emetic Blend containing natural extractssuch as, Scutellaria baicalensis, Lemon and Citrus extracts, Ganoderma Lucidum, Zingiber Officinale, Grape seed extract, Mentha Spicata, Peppermint, Cinnamon etc. can help reduce symptoms of morning sickness without any side effects. It may be present in an amount 50-600mg preferably 200mg.

Bowel regulator:

This is added as it enhances peristaltic movement of intestine and thereby improves digestion during pregnancy A large no. of women suffer from constipation in the third trimester. A bowel regulator, made from safe and natural ingredients, (such as, Hull lignans, Foeniculum vulgare, Senna Alexandrina, Zingiber Officinale, cuminum cyminum, Carum Carvi etc.) soothes their symptom and makes them feel better. It may be present in an amount 50-2000mg preferably, 200mg. UTI blend:

It may be cranberry extract, hibiscus extract or D- manno sewhich possess Anti- adherence properties that prevent fimbriae Escherichia coli from adhering to uroepithelial cells in the urinary tract. It may be given in an amount 50- 800mg.

Choline:

This is important for development of the foetus’s brain and spinal cord. It may be present in an amount 50-500mg.

Amino acids:

These are optional. Amino acids display important role for optimum foetal growth and other necessary functions for continuing fruitful pregnancy. Arginine, glutamine, tryptophan and taurine play a crucial role in foetal growth, development and survival while ornithine and proline are important players for the regulation of gene expression, protein synthesis and angiogenesis.

Prebiotics and probiotics:

Probiotic supplementation has been associated with prevention of gestational diabetes and mastitis. It may be present between 20-200mg.

Inositol:

It helps in conception and managing of gestational diabetes. It may be present between 100

- lOOOmg.

The inventors also noticed that there are some reactions caused by administration of one vitamin may affect the intake of other vitamins. For instance, while magnesium is important for absorption of vitamin D, the amount of magnesium intake is important. Sub-optimal amount may cause some adverse reactions [Advances in Nutrition, Volume 7, Issue 1, January 2016, Pages 25-43]. Similarly, excess amount of vitamin A can cause nausea, vomiting, dizziness, blurred vision, and poor muscle coordination etc. Some studies show that vitamin B6 has an adverse effect on phenytoin [https://www.uspharmacist.com/article/drug- interactions-with-vitamins-and-minerals]. Vitamins A and D when administered singly at high levels adversely affect bone metabolism. However, simultaneous administration of both vitamins at high levels will apparently diminish the toxic effects of each; High levels of dietary vitamin E are also believed to interact with vitamins D and K. It is because of these interactions of the vitamins with each other that the composition of the invention has been developed after much research on each vitamin and their reactions with each as well as with minerals and the proportion chosen is designed to avoid deleterious effects and provide positive nutritional effect. Thus, the compositions and kit developed is synergistic.

Further, in the composition of the invention, Iron is designed to be in Time-Release format - released at a certain period and suited for appropriate absorption by the body. Post Consumption of tablet, 40% Iron is released within the first 2 hours, and subsequently 20% of Iron is released every 2 hours. Therefore, total Iron is released within 8 hours of consumption. Typically, the human body can only absorb only 12-18 mg of Iron at one time and rest of dose is known to pass the intestine without absorption thereby causing black stools, constipation and loss of nutrient material. In this case, when Iron is ‘Time-Released’ it ensures proper absorption of Iron in the body and causing minimum physiological sideeffects.

The metals used in the composition may be in the form of slats. Any specific form of the salt may be used as long as it provides similar elemental or dietary values as described above.

The composition of the invention may be in the form of tablet, capsule, chewable or swallow able composition, (i.e. those that do not readily dissolve when placed in the mouth and may be swallowed whole without any chewing), in the form of a liquid syrup, powders, granules, effervescent tablets, mouth dissolving tablets or strips - or any other pharmaceutical delivery system. Tablet dosage form will be preferred.

Additionally, the composition may be provided with a suitable film coating. The composition may employ suitable excipients and carriers such as polyvinylpyrrolidone, polyvinyl alcohol and acetate, cellulosics such as methyl and ethyl cellulose, hydroxyethyl cellulose and hydroxylpropyl methylcellulose, acrylates and methacrylates, copolymers such as the vinyl- maleic acid and styrene-maleic acid types, and natural gums and resins such as zein, gelatin, shellac and acacia etc.

The composition of the invention may also be formulated as a chewable composition having palatable taste and mouthfeel, are relatively soft and quickly disintegrates in the mouth. The chewable composition may include suitable favorants, sucralose, monoammonium glycyrrhizinate, flavor oils, anise oil, cinnamon oil, vanilla, vanillin, cocoa, chocolate, etc. as may be known to a person skilled in the art.

Finally, dissolution of the compositions may be facilitated by including relatively small particles sizes of the ingredients used. In addition to those described above, any appropriate fillers and excipients may be utilized in preparing the swallow able, chewable and/or dissolvable compositions of the present invention so long as they are consistent with the objectives described herein. For example, binders are substances used to cause adhesion of powder particles in granulations. Such compounds appropriate for use in the present invention include, by way of example and without limitation, acacia, compressible sugar, gelatin, sucrose and its derivatives, maltodextrin, cellulosic polymers, such as ethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, carbo xymethylcellulose sodium and methylcellulose, acrylic polymers, such as insoluble acrylate ammo nio methacrylate copolymer, polyacrylate or polymethacrylic copolymer, povidones, copovidones, polyvinylalcohols, alginic acid, sodium alginate, starch, pregelatinized starch, guar gum, polyethylene glycol and others known to those of ordinary skill in the art. Diluents, lubricants glidants, colorants may be included in the composition if desired.

In an embodiment, the kit may comprise 3 or more compositions for each trimester.

For the purpose of promoting an understanding of the principles of the invention, reference will be made to the embodiments. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated system, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates.

It will be understood by those skilled in the art that the foregoing general description and the following detailed description are explanatory of the invention and are not intended to be restrictive thereof.

Reference throughout this specification to “an aspect”, “another aspect” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase “in an embodiment”, “in another embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such process or method. Similarly, one or more devices or sub-systems or elements or structures or components proceeded by "comprises... a" does not, without more constraints, preclude the existence of other devices or other sub- systems or other elements or other structures or other components or additional devices or additional sub-systems or additional elements or additional structures or additional components.

Multi-micronutrient (MMN) as used herein is a composition comprising various vitamins and minerals for treatment or prevention of specific micronutrient deficiency in pregnant women.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skilled in the art to which this invention belongs. The system, methods, and examples provided herein are illustrative only and not intended to be limiting.

The invention is illustrated by the following examples which are not to be treated as the only illustrations of the invention and any obvious modification would be deemed to fall within the scope of the invention.

EXAMPLE

Preparation of Multi-Vitamin composition- The following ingredients were used to prepare composition comprising multi-vitamin and multi-minerals during the first, second, and third trimesters of pregnancy:

Table 1: MULTI MICRONUTRIENT (MMN), 3-STAGE COURSE

A study is undertaken to evaluate the effectiveness of the compositions of the present invention in the treatment of patients. The objective of the study is to determine whether oral intake of the compositions results in an improvement of the nutritional status of patients with regard to the specific vitamins and minerals contained in the administered compositions. The study was conducted in 5 patients over a period of 6 months. The 5 subjects were pregnant women in the first trimester of their pregnancy. None of them had any severe deficiencies or complications at the beginning of the study. They were administered on the trimester-wise composition for a period of 6 months - from the middle of the first trimester to second trimester to the middle of the third trimester. No other nutritional supplements were taken by the subjects during the assessment period except invented composition.

An assessment of the nutritional status of each woman was conducted at various intervals for a six-month period. A statistically significant improvement in the nutritional status of various vitamin and mineral levels measured is observed in the treated subjects over the controls upon completion of the study. Therefore, the study confirms that oral administration of the compositions of the present invention is effective in improving the nutritional status of patients.

As evident from the table above, the nutritional status of the patient has improved as compared to 1^st reading and maintained within ± 5 margin.

A second study was undertaken in 20 pregnant women for eight months beginning from their first trimester to the third trimester - to assess the effect of the composition of the invention on the symptomatic relief observed in patients after consuming the trimester-wise composition for the entire 3 trimesters. The results are tabulated below:

As seen from the above table 9 of 10 women reported no morning sickness; 7/10 reported low frequency of leg cramps, 8/10 reported no Bloating and Burping and GI,7/10 reported Less Constipation and Black stool, 9/10 reported Less Fatigue, energy and mood swings, 8/10 reported Normal Blood Pressure, 7/10 reported normal blood glucose levels in first, second and third trimesters.

This was a double blinded randomized controlled two arm study with one group treated with the present invention composition and the other with placebo, in addition to the standard of care treatment. Each group had 10 women and the baseline parameters like age, weight and blood pressure were insignificantly different between groups. Majority of the women in either group were without any history of complications. Thus, the kit of the invention provides significant improvement in the nutritional health of the woman.

Although the present invention has been described in considerable detail with reference to certain preferred embodiments thereof, other obvious variants are possible and may be easily devised by a person skilled in the art. Therefore, the spirit and scope of the appended claims is not intended to be limited to the description and the preferred embodiments set out within this specification.

While specific embodiments of the present invention have been described, other and further modifications and changes may be made without departing from the spirit of the invention. All further and other modifications and changes are included that come within the scope of the invention as set forth in the claims. The disclosure of all publications cited above are expressly incorporated by reference in their entireties to the same extent as if each were incorporated by reference individually.

Claims

CLAIM:

1. A kit of nutritional supplements to pregnant women, which comprises: a) a first composition comprising the following ingredients for the first trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron; Omega; and Anti-emetic anti-nausea blend; b) a second composition comprising the following ingredients for the second trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron, Iron, Calcium; Omega; c) a third composition comprising the following ingredients for the third trimester: vitamins A, Bl, B2, B3, B5, B6, B7, B9, B12, C, D, E, K; and Minerals, Zinc, Iodine, Magnesium, Molybdenum, Copper, Selenium, Manganese, Chromium, Boron, Iron, Calcium; Omega; and Bowel Regulator for constipation;

2. A kit as claimed in claim 1 wherein the composition for the first trimaster additionally comprises Iron, Calcium, Choline, Inositol, Pre and Probiotics, and Amino acids.

3. A kit as claimed in claim 1 wherein the composition for the second trimester further comprises Choline, Inositol, Amino acids, Pre and Probiotics.

4. A kit as claimed in claim 1 wherein the composition for the third trimester further comprises (Optionally, Choline, Inositol, Amino acids, Pre and Probiotics, and Urinary Tract Infection blend.

25 A composition useful as nutritional supplement in the first trimester comprising a combination of:

Vitamin A- 600-6000mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to lOOmg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2 -10 mg, preferably lOmg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg;

Vitamin B9- 0.2 to lOmg, preferably 5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg;

Zinc - 10-40mg preferably 12mg;

Iodine - 100-300pg, preferably 200pg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 206mg;

Omega 3 - 50-2000mg, preferably lOOmg;

Anti-emetic anti-nausea blend- 50mg-600mg, preferably 200mg;

Together with nutritionally acceptable excipients; A composition as claimed in claim 5 comprising a combination of:

Vitamin A- 1600mcg;

Vitamin Bl- 1.6mg;

Vitamin B2- 2 mg;

Vitamin B3 -18mg;

Vitamin B5- 5mg;

Vitamin B6 -lOmg; Vitamin B7 -30mcg;

Vitamin B9- 5mg;

Vitamin B12- 3.6mcg;

Vitamin C -60mg;

Vitamin D- 400IU;

Vitamin E -lOmg;

Vitamin K -55 mcg;

Zinc - 12mg;

Iodine -200|ig;

Copper -1.7mg;

Selenium -40mcg;

Manganese -4 mg;

Chromium-50mcg ;

Molybdenum-45mcg;

Boron -150mcg;

Magnesium -206mg;

Omega 3 - lOOmg;

Anti-emetic anti-nausea blend- 200mg;

Together with nutritionally acceptable excipients. A composition useful as nutritional supplement in the second trimester comprising a combination of:

Vitamin A- 600-6000mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to 100 mg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2 -10 mg, preferably 3 mg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg;

Vitamin B9- 0.2 to lOmg, preferably 0.5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg; Iodine - 100-300pg, preferably 200pg;

Zinc - 10-40mg preferably 12mg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 206mg;

Iron - 30-100 mg, preferably 60mg;

Calcium - 300-800 mg, preferably 500mg;

Omega 3- 50-2000mg, preferably 200mg; together with nutritionally acceptable carriers. A composition as claimed in claim 7 wherein the composition comprises:

Vitamin A- 1600mcg;

Vitamin Bl- 1.6mg;

Vitamin B2- 2mg;

Vitamin B3 -18mg;

Vitamin B5- 5mg;

Vitamin B6 -3 mg;

Vitamin B7 -30mcg;

Vitamin B9- 0.5mg;

Vitamin B12- 3.6mcg;

Vitamin C -60mg;

Vitamin D- 400IU;

Vitamin E -lOmg;

Vitamin K -55 mcg;

Iodine -200pg;

Zinc -12mg;

Copper -1.7mg;

Selenium -40mcg;

Manganese -4 mg;

Chromium-50mcg ;

Molybdenum-45mcg;

28 Boron -150mcg;

Magnesium -206mg;

Iron - 60mg;

Calcium -500mg;

Omega 3- 200mg; together with nutritionally acceptable carriers. A composition useful as nutritional supplement in the third trimester comprises a combination of:

Vitamin A- 600-6000 mcg, preferably 1600mcg;

Vitamin Bl- 0.2 to lOOmg, preferably 1.6mg;

Vitamin B2- 0.2 to 100 mg, preferably 2mg;

Vitamin B3 - 2 to 35mg; preferably 18 mg;

Vitamin B5- l-10mg- preferably 5mg;

Vitamin B6 - 2 -10 mg, preferably 3 mg;

Vitamin B7 - lOmcg to lOmg, preferably 30mcg;

Vitamin B9- 0.2 to lOmg, preferably 0.5mg;

Vitamin B12- 0.2 to 1500 mcg, preferably 3.6mcg;

Vitamin C - 30-200 mg, preferably 60mg;

Vitamin D- 200-4000 IU, preferably 400IU;

Vitamin E - 7 to 400mg, preferably lOmg;

Vitamin K - 25-90 mcg, preferably 55mcg;

Iodine - 100-300pg, preferably 200pg;

Zinc - 10-40mg preferably 12mg;

Copper - l-2mg, preferably 1.7mg;

Selenium - 30-70 mcg, preferably 40mcg;

Manganese - 2-6 mg, preferably 4mg;

Chromium- 20-100 mcg, preferably 50mcg;

Molybdenum- 45mcg-2mg, preferably 45mcg;

Boron - lOOmcg -10 mg, preferably 150mcg;

Magnesium - 200-400 mg, preferably 310mg;

Iron - 30-100 mg, preferably 60mg;

Calcium - 300-800 mg, preferably 500mg;

Omega 3- 50-2000mg, preferably 200mg;

Digestive blend- 50mg-600mg, preferably 200mg;

29 together with nutritionally acceptable carriers. A composition as claimed in claim 9 wherein the composition comprises:

Vitamin A- 1600mcg;

Vitamin Bl- 1.6mg;

Vitamin B2- 2mg;

Vitamin B3 -18mg;

Vitamin B5- 5mg;

Vitamin B6 -3 mg;

Vitamin B7 -30mcg;

Vitamin B9- 0.5mg;

Vitamin B12- 3.6mcg;

Vitamin C -60mg;

Vitamin D- 400IU;

Vitamin E -lOmg;

Vitamin K -55 mcg;

Iodine -200pg;

Zinc -12mg;

Copper -1.7mg;

Selenium -40mcg;

Manganese -4 mg;

Chromium-50mcg ;

Molybdenum-45mcg;

Boron -150mcg;

Magnesium -3 lOmg;

Iron -60mg;

Calcium -500mg;

Omega 3- 200mg;

Digestive blend- 200mg; together with nutritionally acceptable carriers.

30