RU2480222C2 - Pharmaceutical preparations containing ferric chelate bisglycinate (2) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, and concerns pharmaceutical preparations containing ferric chelate bisglycinate (2) associated with a mixture of sweetening agents with improved flavour.

EFFECT: invention refers to the use if said preparations in prevention and (or) treatment of pathological conditions caused by ferric deficiency.

12 cl, 4 ex

Description

The iron bisglycinate chelate (2) has the following structural formula

This compound and its structure have been known for some time (S.D. Ashmed, Chemistry of Bisglycine Iron Chelate (2), Ashmed SD, The chemistry of ferrous bis-glycinate chelate, Arch. Latino Am. De Nutr., 2001, 51 (1 ), 7-12; Atkins PW, Berau JA, 1992 General Chemistry 2-ed ed. Scientific American Books, WH Freeman New York; Coplin et al., Tolerability of Iron: a comparison of bisglycinoiron (II) and ferrous sulphate, Clinical Therapeutics, vol. 13, no. 3, 606-612, 1991).

The iron bisglycinate chelate (2) is a highly soluble compound characterized by a metal center, Fe (II), tetra-coordinated by two identical chelating compounds (glycine). Dative bonding of the nitrogen atom contributes to the stabilization energy of the electronic orbitals of the metal center and the geometry of the bonding component through the formation of a pentatom ring.

This compound is also known for its tolerance, safety and high bioavailability (Jeppsen R. B., Toxicology and safety of Ferrochel and other iron amino acids chelates, Arch. Latino Am. De Nutr., 2001, 51 (1), 26-34; yes the opinion that the Scientific Group on Food Additives, Perfumes to Improve Technological Properties and Food Related Materials, upon request from the Commission, refers to iron bisglycinate (2) as a source of iron for use in the manufacture of products and food additives, EFSA Journal, 2006, 299, 1-17).

The literature indicates that such a chelate complex has a greater bioavailability than mineral salts of iron, such as, for example, iron sulfate (2), since it is absorbed by the intestinal mucosa as such and therefore does not undergo any chemical changes in the gastrointestinal tract ( Pineda O. et al. Effectiveness of the iron-amino acid chelate in treating iron deficiency anemia in adolescents, Pineda O. et al., Journal of appl. Nutr., Vol. 46, nos. 1-3, 1994; Pineda O. Effectiveness of treating iron deficiency anemia in infants and young children with bisglycine chelate and iron (2), Pineda O., Nutrition, 17, 2001, 381-84).

The binding stability demonstrated by the fact that the product does not hydrolyze at different pH values of the gastrointestinal tract, and the low molecular weight (204 g / mol) allows maximum absorption when administered orally (de Wayne, H.A. Absorption and metabolism of the chelate iron amino acid, DeWayne HA Arch. Latino Am. De Nutr., 2001, 51 (1), 7-12; Marchetti M. et al. Comparison of the rates of decomposition of vitamins when mixed with metal sulfates or metal-amino acid chelates, Marchetti M., J Food Comp. Anal., 200, 13, 875-884). Such a compound has the most general use as a food supplement, especially for products such as milk and dairy products that do not contain iron.

Such a compound does, however, have a rather unpleasant taste characteristic of the iron complex contained therein and, in a more general sense, for all products containing iron, which are generally well known to be difficult to take.

It has now been unexpectedly discovered that adding to a chelate of iron bisglycinate (2) a certain mixture of sweeteners and flavors in a certain ratio allows you to get a drug with improved taste, eliminating unpleasant taste and, thus, facilitating the reception of the compound.

In particular, these mixtures contain acesulfame potassium, sucralose, sorbitol and flavors of orange and lemon.

The aim of the present invention are, therefore, preparations containing an iron bisglycinate chelate (2) in association with a mixture of potassium acesulfame, sucralose, sorbitol and flavors, preferably orange and lemon, in which the mixture is in a ratio of about 1: 0.30-0 50: 0.12-0.24: 3.0-3.4 by weight, respectively. Preferably, the above ratio is about 1: 0.40: 0.18: 3.20 by weight. The preparations of the present invention may also contain inert fillers and (or) physiologically acceptable additives, such as, for example, acid-forming agents and (or) preservatives (ascorbic acid, methyl para-aminobenzoate).

The iron bisglycinate chelate (2) is present in the preparations of the present invention in an amount that preferably varies from 60 to 400 mg / dose. More preferably, the iron bisglycinate chelate (2) is present in an amount of 70 mg / dose or 210 mg / dose.

The hydrogen index (pH) generated by the preparations of the invention, dissolved in water, is preferably above 4, and more preferably between 4.5 and 7.5.

The above pH is thus generated by dissolving a preparation containing iron bisglycinate chelate (2) in an amount between 60 and 400 mg in 100-150 ml of water.

The preparations of the present invention are preferably intended for oral administration and may more preferably be in the form of a tablet, soft or hard capsule, oral solution, oral suspension, granules, effervescent granules or an oral soluble powder.

Even more preferably, said tablet may be an oral soluble, chewable, effervescent or swallowable tablet.

A further objective of the present invention is the use of a preparation containing iron bisglycinate chelate (2) in association with a mixture containing potassium acesulfame, sucralose, sorbitol and flavors, preferably orange and lemon powder flavors, in a ratio of 1: 0.30-0.50 : 0.12-0.24: 3.0-3.4 by weight, respectively, for the prevention and (or) treatment of pathological conditions caused by iron deficiency.

The following examples are intended to facilitate understanding of the present invention without limiting it in any way.

EXAMPLES

Example 1 Effervescent tablet preparation: Active ingredient: mg / tablet Iron Bisglycinate Chelate (2): 70 mg (corresponding to 14 mg of iron) Sweeteners: Acesulfame Potassium: 25 mg Sucralose: 10 mg Sorbitol: 4,5 mg Flavoring substance Flavoring substance of orange: 80 mg

The ratio of acesulfame potassium: sucralose: sorbitol: the flavoring substance in the tablet according to Example 1 is 1: 0.40: 0.18: 3.20.

The pH of the solution obtained by dissolving the effervescent tablet of Example 1 in 150 ml of water is 4.7.

Example 2 Swallowed tablet: Active ingredient: mg / tablet Iron Bisglycinate Chelate (2): 70 mg (corresponding to 14 mg of iron) Sweeteners: Acesulfame Potassium: 10 mg Sucralose: 4 mg Sorbitol: 1.8 mg Flavoring substance Lemon Powder Flavor: 80 mg

The ratio of acesulfame potassium: sucralose: sorbitol: the flavoring substance in the tablet according to Example 2 is 1: 0.40: 0.18: 3.20.

The pH of the solution obtained by dissolving the tablets of Example 2 in 50 ml of water is 7.0.

Example 3 Effervescent granule preparation Active ingredient: mg / tablet Iron Bisglycinate Chelate (2): 210 mg (corresponding to 42 mg of iron) Sweeteners: Acesulfame Potassium: 25 mg Sucralose: 10 mg Sorbitol: 4,5 mg Flavoring substance Flavoring substance of orange: 80 mg

The ratio of acesulfame potassium: sucralose: sorbitol: a flavoring substance in effervescent granules according to Example 3 is 1: 0.40: 0.18: 3.20.

The pH of the solution obtained by dissolving the effervescent granules of Example 1 in 150 ml of water is 4.7.

Example 4 The drug solution / oral suspension: Active ingredient: mg / tablet Iron Bisglycinate Chelate (2): 210 mg (corresponding to 42 mg of iron) Sweeteners: Acesulfame Potassium: 25 mg Sucralose: 10 mg Sorbitol: 4,5 mg Flavoring substance Flavoring substance of orange: 80 mg

The ratio of acesulfame potassium: sucralose: sorbitol: a flavoring substance in an oral suspension according to Example 4 is 1: 0.40: 0.18: 3.20.

The pH of the oral suspension solution (as such) is 5.5.

EXPERIMENTAL PART

Three different effervescent granule preparations were prepared, each containing the same dose of the active ingredient (70 mg of iron bisglycinate chelate (2)) and a different amount of flavoring and sweetening substances. These three drugs are listed in the table below. Drug number 2 is a drug with sweeteners and flavors in the optimal ratios defined by us (and is the drug claimed by us).

Component Drug 1 Drug 2 Drug 3 Acesulfame
potassium 15 mg 25 mg 35 mg Sucralose 5 mg 10 mg 15 mg Sorbitol 2 mg 4,5 mg 8 mg

These three preparations were tasted by three different people who were asked to judge their taste, expressed in numerical form, according to the table below.

Judgment Flavoring
qualities one Unacceptable 2 Good ones 3 Good ones four Excellent

The judgments expressed by the three entities are summarized in the following table along with estimated averages.

Subject Drug 1 Drug 2 Drug 3 A one 3 2 B 2 four 2 C 2 four 2 Average
value 1.7 3,7 2

The results indicate that drug 2 is the best drug.

Claims (12)

1. A pharmaceutical preparation containing an iron bisglycinate chelate (2) in association with a mixture containing potassium acesulfame, sucralose, sorbitol and flavors, in which the compounds of this mixture are in a ratio of about 1: 0.30-0.50: 0.12 -0.24: 3.0-3.4 by weight, respectively. 2. The drug according to claim 1, in which the specified ratio is approximately 1: 0.40: 0.18: 3.20 by weight. 3. The drug according to claim 1, in which the chelate of iron bisglycinate (2) is present in an amount that varies from 60 to 400 mg / dose. 4. The drug according to claim 3, in which the chelate of iron bisglycinate (2) is present in an amount of 70 mg / dose. 5. The drug according to claim 3, in which the chelate of iron bisglycinate (2) is present in an amount of 210 mg / dose. 6. The drug according to claim 1, in which a dose of the drug containing from 60 to 400 mg of iron bisglycinate chelate (2), dissolved in 100-150 ml of water, generates a pH above 4. 7. The drug according to claim 4, in which the specified pH is between 4.5 and 7.5. 8. The preparation according to claim 1, in which the specified flavoring substance is preferably selected from a powder of flavoring substances of orange and lemon. 9. The drug according to one of the preceding paragraphs in the form of a tablet, soft or hard capsule, oral solution, oral suspension, granules, effervescent granules or powder, soluble in the mouth. 10. The drug according to claim 7, in which the specified tablet is soluble in the mouth, chewable, effervescent or swallowed tablet. 11. The drug according to one of the preceding paragraphs, also containing inert fillers and (or) physiologically acceptable additives. 12. The use of the drug according to claims 1 to 9 for the prevention and (or) treatment of pathological conditions caused by iron deficiency.