DESC:FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

1. TITLE OF THE INVENTION:
NOVEL METHOD FOR PREPARATION OF MICELLAR IRON AND ITS ORAL DOSAGE FORMS
2. APPLICANT:
Name: Amitojas Wellness Private Limited
Nationality: Indian Company
Address: A-810, Shweta Aryan, Pipeline road, Jeedimetla, Ranga Reddy Dist, Hyderabad - 500067, Telangana

3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be performed:

4. DESCRIPTION:
Field of the invention:
[0001] The present disclosure generally relates to the technical field of nutritional supplement, and in specific relates to a process for the preparation of microencapsulated micellar iron supplement composition with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.
Background of the invention:
[0002] In general, iron is required for various key cellular activities and biosynthetic processes in the human body, including oxygen transport capacities, aerobic cellular activity, intracellular electron transport, and fundamental enzymatic reactions inside body tissue. Unfortunately, iron insufficiency is the most frequent recognised kind of nutritional deficiency among humans, due to a combination of socioeconomic situations, environmental variables, genetic predispositions, and collective eating patterns among the general population.

[0003] Anemia, often known as iron deficiency, affects nearly a third of the world's population, both in developing and industrialised nations. It is known to affect people of all ages, but it is more dangerous to children aged 0 to 5, women of reproductive age, and pregnant women. According to a World Health Organization research, iron deficiency causes 50% of all instances of anaemia. Low iron intake, various levels of chronic blood loss, and malabsorption are the primary risk factors for iron deficiency anaemia (IDA). In addition, IDA is usually linked to chronic disorders such as chronic kidney disease (CKD), chronic heart failure, malignancy, and inflammatory bowel disease (IBD). Anemia, or iron deficiency, is recognised to impact a significant number of adult and senior patients in internal medicine departments. Oral iron is generally the first line of treatment since it is a cost-effective way to restore iron balance.

[0004] Intravenous (IV) iron is recommended as second-line therapy for patients who do not respond to oral iron, who have intolerance to oral iron, or who are noncompliant with oral iron therapy, require rapid iron replacement, malabsorption due to surgery, heavy bleeding, concomitant use of erythropoietin, and anemia secondary to cancer or chemotherapy. In spite of their good safety profiles, IV iron preparations are painful, require patient monitoring and carry the risk of anaphylaxis and certain preparations can cause injection site discoloration.

[0005] Currently, inorganic iron supplements such as ferrous sulphate, ferrous oxide, ferric pyrophosphate, and organic chelated iron compounds such as ferrous fumarate, ferrous citrate, Ferric Ammonium citrate, and others are available on the market. When these inorganic iron supplements or organic chelated iron compounds are taken orally, they cause gastric discomfort and constipation by hardening the stools. Further, injectable iron supplements, such as Iron sucrose, Iron dextrose, and others, are also available for IV administration. However, they are inefficient and so unaffordable to the general public. In addition, administering injectable iron supplements necessitates medical help, which complicates the supplementing procedure.

[0006] According to one study, anaemia affects 15% to 75% of people with inflammatory bowel disease (IBD). The most common oral iron supplement used in iron deficiency anaemia (IDA) treatment is ferrous sulphate. Approximately 20% of IBD patients stop taking their medication due to gastrointestinal adverse effects. Oral iron salts are poorly absorbed, resulting in gastrointestinal adverse effects from unabsorbed iron. Oral iron supplements have been designed to be more tolerable in recent years. However, there was still a need for new carriers that not only protect the iron but also enhance its intestinal absorption, thus reducing dosage and side effects.

[0007] Therefore, there is a need for a process for preparation of microencapsulated iron supplement with enhanced stability and increased bioavailability of iron in humans. There is a need for a microencapsulated iron supplement that can be prepared in various oral iron supplements, such as capsules, tablets, sprinkles, syrups, mouth dissolving granules. An Iron supplement without gastrointestinal side effects is the need of the hour. A cost effective and safe alternative iron supplement is needed that does not need medical intervention for the supplementation. There is a need for an iron supplement with good stability profile. There is a need for a microencapsulated iron supplement that is suitable for all age groups including, infants, children, pregnant and lactating mothers and elderly.
Objectives of the invention:
[0008] The primary objective of the invention is to provide a process for the preparation of microencapsulated micellar iron supplement with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.

[0009] Another objective of the invention is to provide a microencapsulated iron supplement in various oral iron supplements, such as capsules, tablets, sprinkles, syrups, mouth dissolving granules.

[0010] The other objective of the invention is to provide an iron supplement that reduces gastrointestinal side effects.

[0011] Yet another objective of the invention is to provide a cost effective and safe alternative for iron supplement that does not need medical intervention.

[0012] Further objective of the invention is to provide an iron supplement with excellent stability profile that can be used for in the preparation of various iron fortified bakery, confectionery and beverage products for general masses.

[0013] Another objective of the invention is to provide a microencapsulated iron supplement that is suitable for all age groups including, infants, children, Pregnant and lactating mothers and elderly.
Summary of the invention:
[0014] The present disclosure proposes a novel method for preparation of micellar iron and its oral dosage forms. The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key/critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0015] In order to overcome the above deficiencies of the prior art, the present disclosure is to solve the technical problem to provide a process for the preparation of microencapsulated micellar iron supplement composition with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.

[0016] According to an aspect, the invention provides a low-cost micellar iron composition with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects. The micellar iron composition comprises 55 to 65 weight percentage of a chelated iron compound, 1 to 4 weight percentage of at least two emulsifiers, 0.5 to 0.9 weight percentage of at least two stabilizing agents, 14 to 19 weight percentage of at least two encapsulating agents, 8.6 to 12.6 weight percentage of at least three coating agents, 0.02 to 3 weight percentage of a mixture of additives, 3.2 to 7.2 weight percentage of a moisturizer, and 1.5 to 3.5 weight percentage of a diluent. The micellar iron composition is provided in various oral dosage forms such as capsules, tablets, oral dispersible granules, food sprinkles, and syrups, thereof.

[0017] In specific, the chelated iron compound includes either ferrous bisglycinate or ferrous triglycinate or iron asparate. The emulsifiers comprise 0.5 to 2 of weight percentage of soya lecithin, and 1 to 2 weight percentage of xanthan gum. The stabilizing agents comprise 0.2 to 0.8 weight percentage of carrageenan, 0.1 to 0.3 weight percentage of mixed tocopherols with anti-oxidant and stabilising properties, along with lipoproteins. The encapsulating agents comprise 10 to 14 weight percentage of calcium caseinate, and 4 to 5 weight percentage of milk phospholipids as micelle forming agents.

[0018] The coating agents comprise 2 to 8 weight percentage of calcium phosphate tribasic, 2.3 to 3.3 weight percentage of sodium & calcium alginates, and 2.3 to 3.3 weight percentage of hydroxy methyl propyl cellulose with stabilising property. The mixture of additives comprise 0 to 0.02 weight percentage of silicon dioxide as anti-caking agent, and 1 to 2 weight percentage of modified corn starch. The moisturizer includes poly dextrin and the diluent includes isomaltulose (palatinose).

[0019] According to another aspect, the invention provides a method for preparation of the micellar iron composition. First, the chelated iron compound is emulsified with the emulsifiers, lipoproteins and the stabilizing agents to obtain a micellar iron core. Next, the micellar iron core is subjected to microencapsulation process for stabilization of the encapsulating agents, the coating agents and the mixture of additives to obtain a microencapsulated iron compound. Finally, the microencapsulated iron compound is dried either through spray drying or agitated thin film drying in an oxygen free environment using inert gases to obtain the micellar iron composition. In specific, the micellar iron composition is in the form of dried micro granules.

[0020] Further, objects and advantages of the present invention will be apparent from a study of the following portion of the specification, the claims, and the attached drawings.
Detailed description of drawings:
[0021] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention, and, together with the description, explain the principles of the invention.

[0022] FIG. 1 illustrates an exemplary method for preparation of a micellar iron composition in accordance to an exemplary embodiment of the invention.
Detailed invention disclosure:
[0023] Various embodiments of the present invention will be described in reference to the accompanying drawings. Wherever possible, same or similar reference numerals are used in the drawings and the description to refer to the same or like parts or steps.

[0024] The present disclosure has been made with a view towards solving the problem with the prior art described above, and it is an object of the present invention to provide a process for the preparation of microencapsulated micellar iron supplement composition with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.

[0025] According to an exemplary embodiment of the invention, a low-cost micellar iron composition is proposed. The micellar iron composition comprises 55 to 65 weight percentage of a chelated iron compound, 1 to 4 weight percentage of at least two emulsifiers, 0.5 to 0.9 weight percentage of at least two stabilizing agents, 14 to 19 weight percentage of at least two encapsulating agents, 8.6 to 12.6 weight percentage of at least three coating agents, 0.02 to 3 weight percentage of a mixture of additives, 3.2 to 7.2 weight percentage of a moisturizer, and 1.5 to 3.5 weight percentage of a diluent.

[0026] In specific, the chelated iron compound includes either ferrous bisglycinate or ferrous triglycinate or iron asparate. The emulsifiers comprise 0.5 to 2 of weight percentage of soya lecithin, 1 to 2 weight percentage of xanthan gum. The stabilizing agents comprise 0.2 to 0.8 weight percentage of carrageenan, 0.1 to 0.3 weight percentage of mixed tocopherols with anti-oxidant and stabilising properties, and lipoproteins. The encapsulating agents comprise 10 to 14 weight percentage of calcium caseinate, 4 to 5 weight percentage of milk phospholipids as micelle forming agents.

[0027] The coating agents comprise 2 to 8 weight percentage of calcium phosphate tribasic, 2.3 to 3.3 weight percentage of sodium & calcium alginates, and 2.3 to 3.3 weight percentage of hydroxy methyl propyl cellulose with stabilising property. The mixture of additives comprise 0 to 0.02 weight percentage of silicon dioxide as anti-caking agent, and 1 to 2 weight percentage of modified corn starch. The moisturizer includes poly dextrin for moisturising and nourishing the dry skin and the diluent includes isomaltulose (palatinose).

[0028] For instance, table 1 depicts an example of the formulation ingredients of proposed composition quantity.

[0029] Table 1:
Ingredient Quantity for 100 g Function of the ingredient
Iron Bisglycinate 59.0 gm Functional Ingredient ( source of Iron)
Soya lecithin 1.0 gm Emulsifier
Xanthan Gum 1.5 gm Emulsifier and stabilising agent
Carrageenan 0.5 gm Stabilizing agent
Calcium caseinate 12.0 gm Micelle forming agent, encapsulating agent
Milk phospholipids 4.5 gm Micelle forming agent, encapsulating agent
Calciumphosphate tribasic 5.0 gm Coating agent
Mixed Tocopherols 0.2 gm Stabilizing agent, Anti-oxidant
Sodium & Calcium alginates 2.8 gm Coating agents
Hydroxy methyl propyl cellulose ( HPMC) 2.8 gm Coating agent, stabilizer
Silicon dioxide 0.01 gm Anti-caking agent
Modified corn starch 1.5 gm Alkaloidss and calcitriol present in the centrum diurnal extract helps in management of eczema, psoriasis, etc..
Poly Dextrin 5.2 gm Moisturizer and nourish the dry skin
Isomaltulose(palatinose) 2.5 gm Diluent
Trisodium Citrate 1.5 gm Buffering agent

[0030] Further, the micellar iron composition is provided in various oral dosage forms such as capsules, tablets, oral dispersible granules, food sprinkles, and syrups, therefore. The micellar iron composition has excellent stability profile that can be used for in the preparation of various iron fortified bakery, confectionery and beverage products for general masses.

[0031] According to another exemplary embodiment of the invention, FIG. 1 refers to an exemplary method 100 for preparation of the micellar iron composition. At step 102, the chelated iron compound is emulsified with the emulsifiers, lipoproteins and the stabilizing agents to obtain a micellar iron core. At step 104, the micellar iron core is subjected to microencapsulation process for stabilization the encapsulating agents, the coating agents and the mixture of additives to obtain a microencapsulated iron compound. In specific, the microencapsulation process involves the formation of a micellar structure with iron in the core. The micellar structure is protected by a lipoprotein layer and stabilized by calcium salts to obtain a microencapsulated iron compound.

[0032] Finally at step 106, the microencapsulated iron compound is dried either through spray drying or agitated thin film drying in an oxygen free environment using inert gases such as nitrogen gas to obtain the micellar iron composition. In specific, the micellar iron composition is in form of dried micro granules. The microencapsulated iron compound is spray dried and granulated for better solubility and stability. The micellar iron composition when used in the oral supplements does not cause any gastric discomfort, while providing highly bioavailable iron.

[0033] According to another exemplary embodiment of the invention, the micellar iron composition has enhanced flow properties, solubility, stability at ambient conditions and increased bioavailability of iron. The micellar iron composition is used for the preparation of oral iron supplements, which includes present composition of iron. The proposed microencapsulated iron compound provides high bioavailable of iron without causing any Gastric distress and reduces the Cost of Iron supplementation, compared to IV- Iron infusions.

[0034] According to another exemplary embodiment of the invention, the present composition of iron is a new oral supplement iron. In one of the comparative studies, results indicate that the high haemoglobin (Hb) is more increased in patients treated with the present composition of iron than who are treated with ferrous sulfate or in the controls. An increase of Hb >2g/ dl is more frequent in patients treated with the present composition of iron than the controls, and is comparable to those patients treated with ferrous sulfate. The present composition of iron is well tolerated in patients with iron deficiency anemia (IDA) and inflammatory bowel disease (IBD).

[0035] The absorption or bioavailability of liposomal pyrophosphate iron is 3.5 times greater than the free pyrophosphate iron, 2.7 times higher than iron sulfate, and 4.1 times higher compared with iron gluconate. The present composition of iron was found to be more effective than iron sulfate in increasing Hb levels and to reduce inflammatory markers in correction of anemia of chronic inflammatory disease. The present composition of iron seems to be a valid alternative to IV iron therapy in chronic kidney disease (CKD) patients.

[0036] The present composition of iron has unique structural, physicochemical and pharmacokinetic characteristics, together with a high iron bioavailability and excellent gastrointestinal tolerance. These properties make the present composition of iron the most suitable formulation for the oral treatment of iron deficiency, even in clinical settings (e.g., chronic kidney disease, cancer, bariatric surgery, etc.), where IV iron seemed to be the only therapeutic option. The present composition of iron (30 mg/day for 15 days, plus 15 mg/day for 75 days) has also been shown to be effective in treating iron deficiency anemia (IDA).

[0037] According to another exemplary embodiment of the invention, preclinical studies conducted on the proposed composition demonstrate that the present composition of iron has unique structural, physicochemical and pharmacokinetic characteristics. The presence of sucrester confers gastroresistance to the present composition of iron, protects its trivalent pyrophosphate iron against enzymatic reduction, and promotes its absorption across the intestinal epithelium by a DMT-1 independent pathway, which is greatly mediated by M cells. All this enables oral present composition of iron to have a high iron bioavailability and a low gastrointestinal toxicity.

[0038] The analysis of available clinical evidence seems to support oral present composition of iron as a new valid opportunity for iron supplementation, which is more comfortable, efficacious (lower doses, higher Hb increments and/or better replenishment of iron stores) and tolerable than traditional oral iron salts. The present composition of iron has been also demonstrated to have a similar effectiveness, with lower risks, in clinical settings where IV iron was the usual treatment option (e.g., CKD, cancer, bariatric surgery, etc.). Thus, the administration of oral present composition of iron emerges as a valuable first option for treating uncomplicated iron deficiency, especially for subjects with intolerance to iron salts or those for which the iron salts are inefficacious.

[0039] Numerous advantages of the present disclosure may be apparent from the discussion above. In accordance with the present disclosure, a process for the preparation of microencapsulated micellar iron supplement composition with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects is disclosed here.

[0040] The proposed microencapsulated iron supplement exhibits enhanced stability and increased bioavailability of iron. The proposed microencapsulated iron supplement is prepared in various oral iron supplements, such as capsules, tablets, sprinkles, syrups, mouth dissolving granules. The proposed iron supplement does not cause gastrointestinal side effects. The proposed microencapsulated iron supplement is cost effective and safe alternative iron supplement. The proposed iron supplement has good stability profile. The proposed microencapsulated iron supplement is suitable for all age groups including, infants, children, pregnant and lactating mothers and elderly.

[0041] It will readily be apparent that numerous modifications and alterations can be made to the processes described in the foregoing examples without departing from the principles underlying the invention, and all such modifications and alterations are intended to be embraced by this application.

Dated this 30th day of December, 2021

Varalakshmi
IN/PA-3287

5. CLAIMS:
We Claim:
1. A micellar iron composition, comprising:
55 to 65 weight percentage of a chelated iron compound;
1 to 4 weight percentage of at least two emulsifiers;
0.5 to 0.9 weight percentage of at least two stabilizing agents;
14 to 19 weight percentage of at least two encapsulating agents;
8.6 to 12.6 weight percentage of at least three coating agents;
0.02 to 3 weight percentage of a mixture of additives;
3.2 to 7.2 weight percentage of a moisturizer; and
1.5 to 3.5 weight percentage of a diluent,
whereby said micellar iron composition is a low-cost iron supplement with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.
2. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said chelated iron compound includes either ferrous bisglycinate or ferrous triglycinate or iron asparate.
3. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two emulsifiers comprise 0.5 to 2 of weight percentage of soya lecithin and 1 to 2 weight percentage of xanthan gum.
4. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two stabilizing agents comprise 0.2 to 0.8 weight percentage of carrageenan, 0.1 to 0.3 weight percentage of mixed tocopherols with anti-oxidant and stabilising properties, along with lipoproteins.
5. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two encapsulating agents comprise 10 to 14 weight percentage of calcium caseinate, 4 to 5 weight percentage of milk phospholipids.
6. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least three coating agents comprise 2 to 8 weight percentage of calcium phosphate tribasic, 2.3 to 3.3 weight percentage of sodium & calcium alginates, 2.3 to 3.3 weight percentage of hydroxy methyl propyl cellulose with stabilising property.
7. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said mixture of additives comprises 0 to 0.02 weight percentage of silicon dioxide as anti-caking agent and 1 to 2 weight percentage of modified corn starch.
8. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said moisturizer includes poly dextrin and said diluent includes isomaltulose (palatinose).
9. The micellar iron composition for nutritional supplement as claimed in claim 1, said micellar iron composition is provided in various oral dosage forms such as capsules, tablets, oral dispersible granules, food sprinkles, and syrups, therefore.
10. A method for preparation of micellar iron composition, comprising:
emulsifying a chelated iron compound with at least two emulsifiers, lipoproteins and at least two stabilizing agents to obtain a micellar iron core;
subjecting said micellar iron core to microencapsulation process for stabilization with at least two encapsulating agents, at least three coating agents and a mixture of additives to obtain a microencapsulated iron compound; and
drying said microencapsulated iron compound either through spray drying or agitated thin film drying in an oxygen free environment using inert gases to obtain a micellar iron composition,
wherein said method provides a low-cost iron supplement composition in oral dosage form with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.
6. DATE AND SIGNATURE:
Dated this 30th day of December, 2021

Varalakshmi
IN/PA-3287

7. ABSTRACT:
Title: Novel Method for Preparation of Micellar Iron and Its Oral Dosage Forms
The present disclosure proposes a process for the preparation of a microencapsulated micellar iron supplement with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects. The proposed micellar iron composition is prepared in various oral iron supplements, such as capsules, tablets, sprinkles, syrups, mouth dissolving granules. The proposed micellar iron composition does not cause gastrointestinal side effects. The proposed micellar iron composition is cost effective and safe alternative iron supplement. The proposed micellar iron composition has excellent stability profile that can be used in the preparation of various iron fortified bakery, confectionery and beverage products for general masses. The proposed micellar iron composition is suitable for all age groups including, infants, children, pregnant and lactating mothers and elderly.

Varalakshmi
IN/PA-3287
,CLAIMS:1. A micellar iron composition, comprising:
55 to 65 weight percentage of a chelated iron compound;
1 to 4 weight percentage of at least two emulsifiers;
0.5 to 0.9 weight percentage of at least two stabilizing agents;
14 to 19 weight percentage of at least two encapsulating agents;
8.6 to 12.6 weight percentage of at least three coating agents;
0.02 to 3 weight percentage of a mixture of additives;
3.2 to 7.2 weight percentage of a moisturizer; and
1.5 to 3.5 weight percentage of a diluent,
whereby said micellar iron composition is a low-cost iron supplement with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.
2. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said chelated iron compound includes either ferrous bisglycinate or ferrous triglycinate or iron asparate.
3. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two emulsifiers comprise 0.5 to 2 of weight percentage of soya lecithin and 1 to 2 weight percentage of xanthan gum.
4. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two stabilizing agents comprise 0.2 to 0.8 weight percentage of carrageenan, 0.1 to 0.3 weight percentage of mixed tocopherols with anti-oxidant and stabilising properties, along with lipoproteins.
5. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least two encapsulating agents comprise 10 to 14 weight percentage of calcium caseinate, 4 to 5 weight percentage of milk phospholipids.
6. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said at least three coating agents comprise 2 to 8 weight percentage of calcium phosphate tribasic, 2.3 to 3.3 weight percentage of sodium & calcium alginates, 2.3 to 3.3 weight percentage of hydroxy methyl propyl cellulose with stabilising property.
7. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said mixture of additives comprises 0 to 0.02 weight percentage of silicon dioxide as anti-caking agent and 1 to 2 weight percentage of modified corn starch.
8. The micellar iron composition for nutritional supplement as claimed in claim 1, wherein said moisturizer includes poly dextrin and said diluent includes isomaltulose (palatinose).
9. The micellar iron composition for nutritional supplement as claimed in claim 1, said micellar iron composition is provided in various oral dosage forms such as capsules, tablets, oral dispersible granules, food sprinkles, and syrups, therefore.
10. A method for preparation of micellar iron composition, comprising:
emulsifying a chelated iron compound with at least two emulsifiers, lipoproteins and at least two stabilizing agents to obtain a micellar iron core;
subjecting said micellar iron core to microencapsulation process for stabilization with at least two encapsulating agents, at least three coating agents and a mixture of additives to obtain a microencapsulated iron compound; and
drying said microencapsulated iron compound either through spray drying or agitated thin film drying in an oxygen free environment using inert gases to obtain a micellar iron composition,
wherein said method provides a low-cost iron supplement composition in oral dosage form with enhanced stability, increased bioavailability of iron in humans and without any gastrointestinal side effects.