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Probiotics Alone Or In Combination With Nutraceutical Supplements , Phytochemicals And/Or Pharmaceutical Substances

Abstract: Title: Probiotics  alone  or  in  combination  with  Nutraceutical Supplements, Phytochemicals and/or Pharmaceutical substances. Abstract: The present invention is a novel pharmaceutical technology of Probiotics alone or in combination with Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances using direct compression technique and moisture resistant coating to provide stable, viable and compatible composition with enhanced bio-absorption of the ingredients.

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Patent Information

Application #
Filing Date
28 February 2014
Publication Number
13/2015
Publication Type
INA
Invention Field
FOOD
Status
Email
Parent Application

Applicants

ESSENZAA LIFESCIENCES LTD.
ESSENZAA LIFESCIENCES LTD. 240, NAMAN PLAZA, ADJACENT TO SHOPPERS STOP, KANDIVALI (W), MUMBAI-400 067.

Inventors

1. MANOJ SHAH
ESSENZAA LIFESCIENCES LTD. 240, NAMAN PLAZA, ADJACENT TO SHOPPERS STOP, KANDIVALI (W), MUMBAI-400 067.
2. SRINIVAS JEGANNATHAN
ESSENZAA LIFESCIENCES LTD. 240, NAMAN PLAZA, ADJACENT TO SHOPPERS STOP, KANDIVALI (W), MUMBAI-400 067.

Specification

Probiotics alone or in combination with Nutraceutical Supplements Phytochemicals and/or Pharmaceutical substances. Field of Invention: The present invention relates to use of direct compression technique and moisture resistant coating for enhanced bio-absorption of Nutraceuticals and stability, viability and compatibility of Probiotics given in conjunction with the Nutraceutical supplements. Background of the invention: The World Health Organization's 2001 definition of Probiotics is "live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host." However, several Probiotic supplements available in the market do not reach in adequate quantities in the intestine, as the live microorganisms are not stable to temperature, gastric acid, humidity, and storage conditions. Besides, the concomitant use of Probiotics with other Nutraceutical supplements remains a challenge owing to compatibility issues. Probiotics have been found to be useful in reduction of lactose intolerance, the inhibition of pathogenic bacteria and parasites, the reduction of diarrhoea, activity against Helicobacter pylori, the prevention of colon cancer, the improvement or prevention of constipation, the in situ production of vitamins, the modulation of blood fats, and the modulation of host immune functions. In such conditions, Nutraceutical supplements play a vital role and may have a possible synergy with Probiotics in enhancing the clinical outcome. Thus, it would be appropriate to provide a synergistic composition of Probiotics and Nutraceutical supplements for enhanced clinical outcome. However, Probiotics are susceptible to temperature, Gastric acid and storage conditions. The objective of the present invention is to overcome the stability, viability and compatibility issues of the Probiotics. There are several examples of Nutraceutical supplements, Phytochemicals and Pharmaceutical substances which can provide synergistic activity when combined with Probiotics. For example, Probiotics enhance the absorption of Calcium and promote bone health. When combined with Iron Supplements, Probiotics can compete with bacterial Siderophore, and thus minimize the chances of bacterial virulence in the gut through iron acquisition. Probiotics can offer enhancing effect along with liver supplements, Protein formulations, etc. When given alone, Probiotics can confer several health benefits. Thus there is a need to preserve the Probiotics in the supplements until they reach the intestine and colonize when given alone or in combination with Nutraceutical supplements. The challenge of developing a synergistic composition is to overcome the compatibility issues of Probiotics Nutraceutical supplements, Phytochemicals and Pharmaceutical substances. Secondly, several Nutraceutical supplements, Phytochemicals and Pharmaceutical substances are varyingly absorbed due to the physiological pH and properties of the substances. For example, minerals such as Calcium and Iron supplements are well absorbed in the acidic medium whereas there are several substances that are acid labile. Thus the present invention is an embodiment of direct compression technique and moisture resistant coating of Probiotics alone or in combination with suitable pH dependent coating of Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances with the benefit of stability, viability and compatibility of Probiotics and enhanced bio-absorption of the ingredients. Prior Art: Giffard and Kendall (US 2005/0079244) disclose a foodstuff in the form of a dried or semi-moist ready-to-eat kibble or powder mix, which contains a combination of a probiotic, prebiotic and a coating of colostrum. Prior to mixing in the food stuff, the probiotic is coated or encapsulated in a polysaccharide, fat, starch, protein or in a sugar matrix using standard encapsulation techniques. Similar to the above disclosure, neither the encapsulating polymers nor the additives used in both core and coating layers have low water vapour and oxygen transmission, and therefore the negative effects of water (humidity) and oxygen cannot be avoided. Accordingly, it has been proposed to dry sugar-based Probiotic systems by foam formation in a very thin layer (Bronshtein WO2005117962), or to use combinations of sugars with a polymeric gelling agent, such as alginate, chitosan, carboxymethyl cellulose or carboxyethyl cellulose. Cavadini et al. (EP 0 862 863) provide a cereal product comprising a gelatinized starch matrix including a coating or a filling. The Probiotic is included with the coating. According to that process, spray- dried Probiotics are mixed with a carrier substrate, which may be water, fat or a protein digest. The mixture is then sprayed onto the cereai product and the whoie product is dried again. Re-hydrating of the already dried bacteria and the additional coating/drying process is costly and damaging to the bacteria. US 2005/0019417 Ai describes a method of preparing products containing moisture- sensitive living microorganisms including Probiotics, comprising at least the steps through which a suspension of Probiotics and a sugar polymer in water miscible solvent is sprayed onto a water soluble, gel-forming solid particles. By these means, the core composed of water soluble gel-forming solid particles may absorb solvent residues and provide protection to Probiotics placed onto said core. Kenneth and Liegh (U.S. Pat. No. 6,900,173) describe the manufacturing of multivitamin protein and Probiotic bar for promoting an anabolic state in a person. The dried Probiotic bacteria are blended in sugar syrup and several other constituents, and the resultant mixture is then extruded and cut into bars. However, the document does not disclose any process or composition that will improve viability or long-term stability of Probiotics in the nutritional bars and there is no indication that the bacteria even survive the process. US 2004/0175389 (Porubcan) discloses a formulation for protecting Probiotic bacteria during passage through the stomach, whilst permitting their release in the intestine. The formulation has also a low water activity and correspondingly long shelf life. The capsule includes a water-free mixture of Probiotic bacteria with monovalent alginate salts, and an enteric coating (e.g., gelatine or celiuiose encapsulation). Upon contact with acidic environment, the outer shell of the capsule turned into a gel, which provides a protecting barrier against proton influx into the capsule core. However, this composition is only useful for tablets and capsules subjected to storage conditions of very low water activity and further require storage in nitrogen-flushed or vacuum-sealed containers. WO 03/088755 (Farber and Farber) describes an oral delivery system for functional ingredients uniformly dispersed in a matrix. The matrix components include a sugar, a carbohydrate, a hydrocolloid, a polyhydric alcohol and a source of mono- or divalent cations. The delivery system is extruded or molded into a final shape with a moisture content of between 15% and 30% by weight. This type of matrix provides very little protection to the Probiotics; the little protection that is provided requires refrigerated conditions, which are not suitable or desirable for many foodstuffs. No description or direction was provided as to how Probiotic bacteria are stabilized during manufacturing or for prolonged storage at room temperatures. McGrath and Mchale (EP 1382241) describe a method of delivering a microorganism to an animal. The micro-organism is suspended in a matrix of cross-linked alginate and cryopreservant (trehalose or lactose, or a combination of both). The matrix is then freeze or vacuum dried to form dry beads containing live Probiotics with shelf-life stability up to 6 months but only under refrigerated conditions. Here again, no description or direction was provided as to how Probiotic bacteria are stabilized during manufacturing or for prolonged storage at room temperatures and high humidity conditions. Ubbink et al. (US 2005/0153018) disclose the preservation of lactic acid bacteria in moist food. The spray-dried bacteria are added to a composition comprising fats, fermented milk powder and saccharides. That composition is then used as the filling of a confectionary product. The subject matter described in that document avoids the detrimental effects of water by embedding the Probiotics in fat or oil rich matrix. However, fat based coating and preserving materials alone do not withstand oxygen and long term exposure to humid conditions. None of the above compositions provide a mixture that can effectively protect the Probiotic in both drying processes and long-term storage at ambient temperatures and varying degrees of humidity. In addition, none of the above compositions provide a mixture that can effectively protect the Probiotics against oxygen which is a main cause for poor stability for long time in storage conditions causing very limited shelf life. EP 2648528 Al describes a composition comprising Probiotic bacteria, the composition comprising: (a) a core composition containing the Probiotic bacteria and a stabilizer, wherein the total amount of Probiotics in the mixture is from about 10% to about 90% by weight of the core composition; (b) an innermost coating layer, layered on said core composition, comprising at least one hydrophobic solid fat or fatty acid having a melting point lower than 60° C; (c) an intermediate coating layer layered on said innermost coating layer, which when present in an aqueous solution in the amount of 0.1% weight/weight over the weight of the solution, has a surface tension lower than 60 mN/m, when measured at 25° C; and (d) an outer coating layer, layered on said intermediate coating layer; wherein the composition is in the form of particles; food products containing the composition and methods of preparation thereof. Gaps in the Prior Art It's evident from the Prior Art that research has been carried out to provide viable Probiotics but none of the earlier inventions have considered the concomitant use of Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances, without compatibility issues. Besides, most of the processes described in the Prior Art are quite expensive on industrial scale and may not provide the desired end result of viability. For example, microencapsulation of Probiotics has been discussed much but the process of spray drying involving high pressure and temperature may destroy the Probiotics. Another example is the Lyophilisation which is very expensive process. Summary of the invention: Probiotics are vulnerable to atmospheric conditions like humidity, heat, and storage conditions and biological hostile conditions due to the presence of gastric acid. Therefore, there is an urgent need for a composition that can effectively protect the Probiotics during manufacturing, long-term storage at ambient temperature, humidity and oxygen and during gastrointestinal passage, either alone or when given concomitantly with Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances. The present invention, in at least some embodiments, overcomes these drawbacks of the background art and provides a solution to these needs, with direct compression technique and moisture resistant coating of Probiotics alone or in combination with Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances, for stable, viable and compatible Probiotics and enhanced bio-absorption of ingredients. Objectives: The first objective of the present invention is to enhance the compatibility of Probiotics with that of Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances for enhanced clinical outcome. The second objective of the present invention is to provide stable Probiotics when given alone or in combination with Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances. The third objective of the present invention is to provide viable Probiotics when given alone or in combination with Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances. Another objective of the present invention is to make the Probiotics stable to changes in temperature, humidity and oxygen, during processing/manufacturing or on storage or while in gastric transit. Yet another objective of the present invention is to provide pH dependent coating of Nutraceutical supplements, Phytochemicals and/or Pharmaceutical substances for better bio-absorption. One more objective of the present invention is to provide moisture resistant coating to protect the moisture sensitive contents in the formulation. Further objective of the present invention is to provide the formulation in powder form, granules, tablets, capsules, suspension, ointments, paste, gel, lozenges, chewable tablets, vaginal tablets, suppositories or enteric feeding for critical conditions. Detailed Description of the Invention There has been a significant growth of using Probiotics due to the excellent health benefits but many formulations do not provide enough clinical outcome. Further, Probiotics are generally not compatible with several Pharmaceutical substances. Besides, several pharmaceutical substances do not get absorbed properly in the body due to physiological and pharmaceutical factors. Thus there is a need to innovate the delivery method of Probiotics with pharmaceutical substances for synergistic composition in a cost-effective manner. Oral administration of Pharmaceutical substances is the most convenient method for patients. It's well known that capsules have a limitation for volume while tablets can accommodate drug volume as high as 1600 mg. Besides, it's possible to provide novel technologies to enhance the bio-absorption of ingredients and achieve greater stability of the pharmaceutical substances. Therefore the prime focus of the present invention is to develop tablet dosage form for enhanced bio-absorption and stability. However, the invention also embodies techniques for other dosage forms such as powder form, granules, capsules, suspension, ointments, paste, gel, lozenges, chewable tablets, vaginal tablets, suppositories or enteric feeding for critical conditions. Direct Compression method is the most advanced and perhaps the simplest manufacturing method with several merits such as process economy, elimination of heat and moisture for better stability, good flow properties, particle size uniformity, better dissolution rates, and batch-to-batch consistency. In the present invention, contents excluding Probiotics are compacted using slugging method, preferably in a roller compactor. Additionally pH dependent polymeric coating is carried out for acid labile contents. Subsequently, the slugged contents are mixed with Probiotics in a double cone blender. The blended powder is then compressed at a low compression force to ensure protection of Probiotics. Manufacturing process in detail with flow chart Check RM (active & 1 excipients) Warehouse ready for dispatch i i Keep aside Lubricant. Add to final blending Sift #40 ,i t < Strapping Transfer to blender (except lubricant) t Shipper packing i < i i Mix 20 mts 'i Printed carton pack Collect in container transfer to compaction 9 ( IPQC \ i, V (1"9' / Shrink pack r Compaction „ 2 8 Blister packing ■ ' p. Multi mill - granulation (*J i > ' i Transfer to packaging Final sieving 3 Crush & sieve retention 1 r ' Final Blending Bulk collects in container coated -polished) ' 4 Collect in drum _ 6 i Polishing Tablet Compression Coating solution preparation i . \ H Collect in container Coating (uncos real Product Name: Ostcni* Pln> Tablets Analysis Date: 29/1J/2014 Dt'Iaih, ol Product: IPQC tvaluation Batch No: 8 001 Batch Site. 50,000 Mfg. Oate: 12/2014 l.pO.ilc: 11/2016 St.No: Parameters Specification Result BUND 1 flow Properties ol Powder • Carr's index • Hausner's ratio J2-21S 1.12-126 fair 18 8 K 121 2 Moisture content NMT 5K 4.5 % TABLETS Description light yellow colored biconve< capsule shaped film-coated tablets with one side break-line and other side plain light yellow colored biconve« capsule shaped film-coated tablets with one side break-line and other side plain Uniformity of Weight NMTSX Complies I Shape Capsule (oblong) Capsule (oblong) 4 Mean weight 1 52 10 03 g ISO g S Hardness 5 II kg/cm' S kg/cm' 6 Friability

Documents

Application Documents

# Name Date
1 716-MUM-2014-FORM 9-02-03-2015.pdf 2015-03-02
2 716-MUM-2014-FORM 3-02-03-2015.pdf 2015-03-02
3 716-MUM-2014-FORM 2(TITLE PAGE)-02-03-2015.pdf 2015-03-02
4 716-MUM-2014-FORM 2 -02-03-2015.pdf 2015-03-02
5 716-MUM-2014-FORM 18-02-03-2015.pdf 2015-03-02
6 716-MUM-2014-DESCRIPTION(COMPLETE)- 02-03-2015.pdf 2015-03-02
7 716-MUM-2014-CORRESPONDENCE-02-03-2015.pdf 2015-03-02
8 716-MUM-2014-CLAIMS-02-03-2015.pdf 2015-03-02
9 716-MUM-2014-ABSTRACT-02-03-2015.pdf 2015-03-02
10 716-MUM-2014-FORM 2.pdf 2018-08-11
11 716-MUM-2014-FORM 2(TITLE PAGE).pdf 2018-08-11
12 716-MUM-2014-FORM 1.pdf 2018-08-11
13 716-MUM-2014-DESCRIPTION(PROVISIONAL).pdf 2018-08-11
14 716-MUM-2014-CLAIMS.pdf 2018-08-11
15 716-MUM-2014-FER.pdf 2019-06-25
16 716-MUM-2014-FORM 4(ii) [24-12-2019(online)].pdf 2019-12-24

Search Strategy

1 2019-06-2514-20-49_25-06-2019.pdf