CN102006868A - Iron and zinc based pharmaceutical formulation for iron deficiency treatment - Google Patents

Abstract

The present invention relates to a pharmaceutical preparation, more particularly, a pharmaceutical preparation capable of providing high iron absorption useful for the prevention and treatment of iron deficiency and iron deficiency anemia of various causes.

Description

Iron- and zinc-based pharmaceutical preparations for the treatment of iron deficiency

technical field

The present invention relates to a pharmaceutical preparation, more particularly, a pharmaceutical preparation providing high iron absorption useful for the prevention and treatment of iron deficiency and iron deficiency anemia of various causes.

Background technique

Hemoglobin is a protein that transports oxygen in the blood, and iron is a component that constitutes the basic structure of hemoglobin, and plays an important role in the process of combining oxygen inhaled by the lungs with hemoglobin and delivering it to tissues, so for It is an essential element for normal tissue growth in humans. Iron is not present in adequate amounts in food, and if iron is ingested exogenously, it may cause various disorders due to the difficulty of absorption. For example, anemia associated with iron deficiency is a common symptom in blood disorders and occurs when the hemoglobin level in the blood falls below a lower limit.

In addition, iron deficiency is the most frequently occurring worldwide nutritional problem, with approximately 30% of the global population suffering from iron deficiency anemia. Iron deficiency is also an important public health problem, not only in less developed countries, but also in vulnerable groups (infants, adolescents, pregnant women and socioeconomically disadvantaged ethnic groups) in developed countries. According to a report published by the World Health Organization (WHO), the incidence rates of iron deficiency anemia in developing and developed countries are 36% and 8%, respectively.

Prevalence of Iron Deficiency Anemia: It is the most common cause of anemia in the world. Thirty percent of the world's population suffers from anemia and at least half of this proportion is due to iron deficiency.

Infants, young children and pregnant women constitute the groups most at risk of anemia. The prevalence of anemia in infants and young children was 43%, and that in pregnant women was 51%. The prevalence of anemia was 37% among school-age children, 35% among non-pregnant women, and 18% among adult males. There are no established prevalence figures for adolescents and older adults. The prevalence in adolescents is generally considered to be similar to that in adult females.

Although iron deficiency anemia is associated with a variety of causes, it is more common in societies with lower socioeconomic levels and poor dietary habits. Causes of anemia may include: delays in taking dietary supplements, infants taking too much milk, vegetarian nutrition, misuse of weight loss diets, and eating disorders, among others. In addition, acute or chronic blood loss, such as ulcerative or menstrual bleeding and parasitic infection, will increase iron requirements, especially during the rapidly growing first year of life and adolescence, leading to Possible cases of anemia.

Large amounts of iron will be present in the gut during oral therapy, causing oxidative damage. Thus, the formation, elimination and function of intestinal mucosal cells will be affected. Zinc ensures the stability of intestinal cells and cell walls, thus providing protection against iron peroxidative damage. Studies have reported that the presence of zinc in the vehicle reduces the formation of iron-dependent hydroxyl radicals in the intestinal mucosa and protects cells against iron-dependent lipid peroxidative damage.

However, in the case of zinc deficiency, the intestinal villi pulp appears atrophied, flattened and blunted, leading to the deterioration of the absorption function of the intestine. In the case of obvious zinc deficiency, the treatment of iron deficiency cannot obtain satisfactory results. In fact, frequent relapses occur in the treatment of anemia due to inadequate absorption of iron and due to failure to obtain sufficient iron stores.

If zinc is used together with iron, it is known to maintain an iron:zinc ratio of 1:1 to 2.5:1 in order to avoid interference of the two elements with adverse absorption.

Folate cannot be produced in the body because PABA cannot be synthesized and the initial glutamic acid cannot be incorporated into the molecule. Folic acid plays a role in the process of cellular DNA synthesis and is an essential substance during the formation of new cells. It is also needed for the regeneration of red blood cells during anemia. In the absence of folic acid, cells will be destroyed and regenerated rapidly, resulting in the deterioration of cell metabolism. The most sensitive cells are normal red blood cells, white blood cells, platelets and intestinal epithelial cells, which divide and regenerate the fastest. Affecting red blood cells can lead to megaloblastic anemia. Megaloblastic anemia, neural tube and other congenital birth defects, and hyperhomosysteinemia may occur in folic acid deficiency.

Vitamin C is a water-soluble and potent antioxidant that cannot be synthesized by the body and plays a supporting role in the absorption of iron. It plays a role in carnitine synthesis, conversion of tryptophan to serotonin and thyroxine, conversion of corticosteroids and aldosterone cholesterol to bile acids, immune system function, cancer prevention, and collagen synthesis effect.

Application WO 2006024241 discloses an attempt to study the prevention and treatment of iron deficiency diseases. WO2006024241 discloses a tablet or aqueous suspension preparation, which can be used to prevent or treat iron deficiency. The preparation contains 6-26% ferrous fumarate, 74-94% powder form hemoglobin extract (haemoderivative), iron ion/ The ratio of heme iron is 30-70%, and the amino acid concentration is 20-30 μmol/100 μmol protein.

Patent JP 2006193428 discloses a preventive or ameliorating agent for the treatment of iron deficiency anemia, comprising compounds containing various iron salts, such as ferrous fumarate, eleuthero extract, and rutin and/or rutin Ding derivatives.

Contents of the invention

The object of the present invention is to provide a pharmaceutical preparation useful for the effective prevention and treatment of iron deficiency and iron deficiency anemia which ensures a high iron absorption.

Another object of the present invention is to provide an effective basic element supplement of iron, zinc and folic acid, in proportions which do not interfere with each other's absorption, against malnutrition-related macrocytic anemia, anemia due to hemorrhage , zinc deficiency concurrent with iron deficiency, and zinc deficiency concurrent with megaloblastic anemia.

Another object of the present invention is to provide effective iron absorbers which are resistant to iron deficiency and latent iron deficiency during pregnancy, infancy and childhood.

The pharmaceutical preparation according to the invention preferably comprises 3-20 mg/ml iron, 1-20 mg/ml zinc, 1.5-60 mg/ml vitamin C and 0.015-0.50 mg/ml folic acid. A preferred pharmaceutical formulation of the invention comprises 5-12 mg/ml iron, 4-10 mg/ml zinc, 5-40 mg/ml vitamin C, and 0.08-0.40 mg/ml folic acid. The most preferred pharmaceutical formulation of the present invention comprises 7-9 mg/ml iron, 5-7 mg/ml zinc, 10-20 mg/ml vitamin C and 0.1-0.2 mg/ml folic acid. According to a preferred formulation of the present invention, the amount of fructose can be maintained between 30mg/ml-250mg/ml, between 100mg/ml-200mg/ml in a preferred formulation, and 120mg/ml-200mg/ml in a most preferred formulation. Between 180mg/ml.

The formulations according to the invention also contain excipients or adjuvants such as sorbitol, sodium saccharin, fructose, sodium hydroxide, paraben, sodium saccharin, neohesperidin dihydrochalcone, orange, lemon and mandarin Fragrance Citric Acid Auxiliary, and Deionized Water.

Formulations according to the invention may also contain mixed sugar materials that may be used in place of fructose, such as sucrose, glucose, mannose, galactose, lactose, or mixtures thereof.

Fructose in the above proportions can form iron-fructose complexes with iron, thereby improving solubility and iron absorption.

The excipient citric acid also plays a similar supporting role in the absorption of iron, while also lowering the pH and acting to maintain the stability of vitamin C. According to a preferred formulation of the present invention, the amount of citric acid is between 1.5mg/ml-600mg/ml, in a more preferred formulation, this amount is between 50mg/ml-300mg/ml, in the most preferred formulation Medium is between 90mg/ml-110mg/ml.

The preparation may also contain other organic acids having one or more carboxyl groups and organic acid side chains, such as tartaric acid, malic acid, as a substitute for citric acid in the preparation according to the invention.

The iron used in the pharmaceutical preparations according to the invention is ferrous iron (Fe(II)) based on its high absorption ratio, but this does not exclude the possibility of using ferric iron (Fe(III)) outside the scope of the invention . The forms of iron and zinc contained in the preparations according to the invention are preferably ferrous fumarate form (C ₄ H ₂ FeO ₄ ) iron salt and zinc sulfate (ZnSO ₄ ) zinc salt, respectively.

Iron salts may also be in the form of ferrous gluconate, ferrous succinate, ferrous glutamate, ferrous lactate, ferrous citrate, ferrous tartrate, ferrous pyrophosphate. According to a preferred embodiment of the present invention, the source of iron is in the form of iron-EDTA, iron ammonium orthophosphate, iron II ammonium iron sulfate complex.

In another preparation according to the invention, the source of iron is iron III protein succinate, iron III polymaltose, iron III sodium-EDTA, carbonyl iron, iron chloride.

The zinc salt may be in the form of anhydrous zinc sulfate or zinc sulfate heptahydrate, zinc acetate, zinc carbonate, zinc chloride, zinc gluconate, zinc picolinate.

The formulation according to the invention is preferably in the form of a syrup, but it can also be prepared as any oral liquid formulation, including aqueous suspensions. Thus, oral administration is more convenient than tablet form, especially for children. The "liquid formulations" also include effervescent tablet compositions, which are also convenient for oral administration once they are dissolved in water.

The ingredients that make up an exemplary composition according to the invention are as follows:

             

Ingredients Amount of syrup per 5ml (mg)

             

Ferrous Fumarate 121

Zinc sulfate 66

Folic acid 0.2

Vitamin C 50

             

Example 2

               

Ingredients Amount of syrup per 5ml (mg)

               

Ferrous Fumarate 121

Zinc sulfate 66

Folic acid 0.2

Vitamin C 50

Fructose 750

               

Example 3

             

Ingredients Amount of syrup per 5ml (mg)

             

Ferrous Fumarate 121

Zinc sulfate 66

Folic acid 0.2

Vitamin C 50

Fructose 750

Citric acid 500mg

             

Example 4

             

Ingredients Amount of syrup per 5ml (mg)

             

Ferrous Fumarate 121

Zinc sulfate 66

Folic acid 0.2

Vitamin C 50

Sorbitol 1500

Propylene Glycol 250

Ethanol 250

Sodium Paraben M 5

             

Example 5

Example 6

             

Ingredients Amount of syrup per 5ml (mg)

             

Ferrous fumarate 121

Zinc sulfate 66

Folic acid 0.2

Vitamin C 50

Sorbitol 1500

Propylene Glycol 250

Ethanol 250

Sodium paraben M 5

Sodium saccharin 5

Sunset Yellow 0.03

Orange Flavor 2

lemon essence 2

Citrus flavor 2

Grapefruit essence 2

Deionized water to make up to 5ml

             

The ratio of iron to zinc in the preparations according to the invention is preferably 1 to 2.5, the ratio of vitamin C to iron is preferably 0.5 to 3, and the ratio of folic acid to iron is preferably 0.005 to 0.025. In another preferred formulation according to the invention, the ratio of iron to fructose is preferably 0.04 to 0.1, and the ratio of vitamin C to citric acid is 1 to 10.

Claims (15)

CLAIMS 1. A pharmaceutical preparation for preventing and treating iron deficiency and iron deficiency anemia, characterized by comprising 3-12 mg/ml iron, 1-12 mg/ml zinc and 1.5-36 mg/ml vitamin C as active ingredients. 2. The formulation according to claim 1, characterized in that it also contains 0.015-0.3 mg/ml folic acid. 3. The formulation according to claims 1 and 2, wherein the amount of iron is 5-10 mg/ml, zinc 4-9 mg/ml, vitamin C 5-30 mg/ml and folic acid 0.08-0.25 mg/ml. 4. The formulation according to claims 1 and 2, wherein the amount of iron is 7-9 mg/ml, zinc 5-7 mg/ml, vitamin C 10-20 mg/ml and folic acid 0.1-0.2 mg/ml. 5. A formulation according to any one of the preceding claims, further comprising fructose, preferably in an amount of 30-300 mg/ml, more preferably 100-200 mg/ml, most preferably 120-180 mg/ml. 6. The formulation according to any one of the preceding claims, further comprising citric acid, preferably in an amount of 1.5 to 600 mg/ml, more preferably 50-300 mg/ml, most preferably 90-110 mg/ml. 7. Preparation according to any one of the preceding claims, characterized in that the iron contained in the preparation is in the form of an iron salt selected from the group consisting of ferrous fumarate, ferrous gluconate, ferrous succinate, glutamic acid Ferrous, ferrous lactate, ferrous citrate, ferrous tartrate, ferrous pyrophosphate. 8. Preparation according to any one of the preceding claims, characterized in that the iron contained in the preparation is in the form of an iron complex selected from the group consisting of iron-EDTA, iron ammonium orthophosphate, iron II ammonium sulfate. 9. Preparation according to any one of the preceding claims, characterized in that the iron is selected from the group consisting of iron III protein succinate, iron III polymaltose, iron III sodium-EDTA, carbonyl iron, iron chloride. 10. Preparation according to any one of the preceding claims, characterized in that the zinc contained in the preparation is in the form of a zinc salt selected from the group consisting of zinc sulfate anhydrous or zinc sulfate heptahydrate, zinc acetate, zinc carbonate, zinc chloride , zinc gluconate, zinc picolinate. 11. The formulation according to any one of the preceding claims, further comprising an excipient or an auxiliary material selected from the group consisting of sorbitol, propylene glycol, ethanol, sodium saccharin, fructose, sodium hydroxide, paraben, sodium saccharin, new orange Dermoglobin Dihydrochalcone, Orange, Lemon, and Mandarin Flavours, Sunset Yellow, and Deionized Water. 12. The formulation according to any one of the preceding claims, characterized in that the formulation is an oral liquid formulation, including syrup dosage forms and aqueous suspension dosage forms. 13. The preparation according to claim 12, characterized in that said oral liquid preparation further comprises a liquid composition which can be administered orally obtained when the effervescent tablet is dissolved in water. 14. Preparation according to any one of the preceding claims, characterized in that the ratio of iron and zinc in said preparation is preferably 1 to 2.5, the ratio of vitamin C to iron is preferably 0.5 to 3, the ratio of folic acid and iron is preferably 0.005 to 0.025. 15. Preparation according to any one of the preceding claims, characterized in that the ratio of iron and fructose in said preparation is 0.04 to 0.1.