WO2024038361A1

WO2024038361A1 - Oral composition for breastfeeding mothers and use thereof

Info

Publication number: WO2024038361A1
Application number: PCT/IB2023/058129
Authority: WO
Inventors: Ewa Wietrak; Marta Popiel; Natalia Filipowicz
Original assignee: Nutropharma Spolka Z Ograniczona Odpowiedzialnoscia
Priority date: 2022-08-16
Filing date: 2023-08-11
Publication date: 2024-02-22
Also published as: PL442022A1

Abstract

The subject of the invention is an oral, lecithin-comprising composition for breastfeeding mothers, characterized in that it further comprises bromelain and that lecithin is deoiled. The object of the invention is also the use of the composition according to the invention to support and/or improve lactation, preferably in conditions of obstructed milk flow and/or mastitis.

Description

Oral composition for breastfeeding mothers and use thereof

The object of the invention is an oral, lecithin-comprising composition for breastfeeding mothers, characterized in that it further comprises bromelain and that lecithin is deoiled, and use of the inventive composition to support and/or improve lactation.

Exclusive breastfeeding up to at least 6 months of age is a recommended model for infant feeding, recognized by all scientific societies and authorities in the fields of health, paediatrics and nutrition, including among others the WHO, the American Academy of Paediatrics or the Ell Directorate of Public Health. It is a food that is unique and perfectly adapted to nutritional needs of the infant. Breast milk not only has a nutritional function, but also protects the child against, among other things, necrotizing enterocolitis or generalized infection (sepsis), and influences a proper development of brain and retina. It is estimated that 1.4 million children can be saved each year through appropriate breastfeeding practices [1], Due to the fact that the mother's milk provides child's body with many immunoactive components, it is possible to shape proper development of child's immune system. In addition to the health benefits for the child and mother, breastfeeding has a significant effect on a social aspect (it has been shown that mothers who breastfeed have fewer symptoms of depression than those who formula feed) and an economic aspect. As research shows, breastfeeding equally benefits family, local community and state. A study was conducted in US which concluded that if 90% of mothers exclusively breastfed their children for the first 6 months, the savings would run into billions of dollars [2], This means that breastfeeding is an extremely effective investment in future health of children, as well as in their intellectual development, which ultimately generates savings for the family and the state [3], Data collected in 2011 in Gdansk (Poland) show that infants who are fed artificially require more medical visits and are more often subjected to antibiotic therapy, while the costs of their treatment incurred by parents are higher [4], Also, an annual expenditure of the Polish National Health Fund on the reimbursement of milk-substitute formulas is high, amounting to PLN 76,000,000 in 2012. Breastfeeding should therefore be considered not only in terms of benefits for the child and the mother, but also in terms of public healthcare.

In lactating women, there may be conditions of obstructed milk flow and its retention in milk ducts. Recurrent plugged milk ducts occur in 2/3 of breastfeeding women [5], This condition is a common predictor of breast engorgement and mastitis [6], as it can result in growth of unfavourable bacteria for which milk provides a medium. As the data show, breast pain caused by stasis and/or mastitis is one of the reasons for breastfeeding cessation [3], Despite this widespread prevalence as well as serious health and social implications, no convenient, non- pharmacological and scientifically sound method of supporting and improving lactation has been described in literature so far, let alone offered to breastfeeding mothers, particularly in the conditions of obstructed milk flow and/or mastitis.

On one hand, home solutions for such conditions include warm compresses and breast massages. However, such methods are not well grounded in science and are treated as ad hoc measures. Often, used on their own, they are insufficient and encourage breastfeeding mothers to use pharmacological agents either in parallel or afterwards.

On the other hand, conventional medicine, despite its scientific basis and effectiveness, has its significant limitations of use in breastfeeding mothers. Current medical recommendations are based on the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) or antibiotics. Meanwhile, first of all, the use of medicines during pregnancy and lactation is not recommended due to their penetration into the milk and their influence on the child’s health. Accordingly, prolonged or occasional use of NSAIDs or antibiotics is associated with danger to the child and stress for the breastfeeding mother. Secondly, prolonged use of NSAIDs is associated with an increased risk of side effects, such as gastric ulcers. In fact, prolonged ingestion of NSAIDs is discouraged in all patients. In addition, NSAIDs are not classified as anti-oedematous drugs and inhibitors of the growth of microorganisms which may be, among others, a cause of mastitis during lactation. On the contrary - they may reduce the effectiveness of administered antimicrobial drugs [7], Consequently, antibiotics are used to control the developing mastitis. Thirdly, the use of antibiotics by breastfeeding mothers is, as a general rule, avoided. Antibiotic therapy can lead to intestinal dysbiosis and requires gastroprotective therapy. Finally, the widespread use of antibiotics leads to antibiotic resistance in bacteria. The World Health Organization (WHO) estimates that more than 700,000 people worldwide die each year due to antibiotic resistance, and this figure could rise to 10 million by 2050 [8],

A document by Lauwers, J., Swisher, A. Counselling the nursing mother: A lactation consultant’s guide. (5th ed.) Sudbury (MA): Jones & Bartlett. (2011) is well worth mentioning here, revealing lecithin as an agent to help with recurrent milk duct plugging [9], Lecithin dosage recommended therein is one tablespoon 3- 4 times a day, or one to two capsules (1200 mg each) 3-4 times a day. The use of lecithin increases an amount of polyunsaturated fatty acids in breast milk, which reduces viscosity of the milk and facilitates its outflow by reducing milk duct plugging. Unfortunately, the above document does not solve the above-mentioned problems. Firstly, there are various sources of lecithin, which - in practice - are characterized by different nutritional and health values (for more see paragraph below). The most common lecithins on the market are those derived from chicken eggs, soybean and sunflower. Lecithin can also be obtained from rapeseed, flax, hemp and cotton. Since the disclosure does not suggest favourable examples of lecithin, for those of ordinary skill in the art it signifies a choice based primarily on availability and ethical limitations (plant vs. animal lecithin). Secondly, ingestion of a tablespoon of lecithin 3-4 times a day may be associated with low acceptance for the breastfeeding mother. Lecithin received in this way is in the form of a thick oil with a dark brown colour and a specific smell. Eventually, prolonged intake of large amounts of oily substances - e.g. in the form of eight 1 ,200 mg capsules - can have a strong laxative effect.

Due to its higher availability and lower price, the most commonly used plant lecithin today is soybean lecithin. However, due to its allergenic potential and growing concerns about its sustainable cultivation and genetic modification, as well as the fact that introducing soybean lecithin into a high-fat diet may lead to the development of chronic inflammation (in vivo studies), alternative sources of plant lecithin are being sought [10,11 ,12], Among plant-derived lecithins, rapeseed lecithin is less commonly used, but its share in the European market is steadily growing. This is due to the fact that rapeseed lecithin has a higher content of polyunsaturated fatty acids and a lower content of saturated fatty acids compared to soybean lecithin [13,14], In addition, in vivo studies indicate that rapeseed lecithin, in contrast to soybean lecithin, contributes to a greater diversity of bacteria in the gastrointestinal tract [15], Vast majority of commercially available lecithin is in liquid form, which means that it has a lower content of health-promoting phospholipids and a relatively high content of mother oil, mainly in the form of triglycerides [16] whose high dietary supply may be associated with an increased risk of atherosclerosis and cardiovascular events.

A dedicated preparation for plugged milk ducts, Legendairy Milk® Sunflower Lecithin in the form of soft capsules filled with sunflower lecithin in liquid form, is commercially available. One capsule contains 1200 mg of sunflower lecithin and is indicated for use 3 to 4 times a day. In addition to the aforementioned problems of long-term consumption of large amounts of oily substances, nutritional and health benefits of lecithins in oil form, oil-containing preparations face other technical problems. Oils are susceptible to UV light exposure and oxidation. Their long-term stability requires addition of preservatives and special storage conditions. Additionally, sunflower lecithin alone is not the most preferred source of lecithin (more later herein).

Finally, the abovementioned disclosures do not solve the problem of the mastitis condition and, in particular, do not provide a product comprising substances resulting in support and improvement of lactation both in obstructed milk flow and mastitis conditions. As described below, supporting and improving lactation in the mastitis condition can be achieved by providing a product containing bromelain. However, simultaneous administration of lecithin in liquid form and bromelain is difficult or impossible due to the formulation and technological limitations of such a composition. This is because lecithin in liquid form is available in soft gelatin capsules (softgel). Two-part, hard capsules typically used for encapsulating medicines and dietary supplements make it impossible to encapsulate liquids, and the available encapsulation technologies are uneconomical. On the other hand, bromelain, which is an enzyme breaking down, among other things, the gelatine of which the softgel capsule shells are made of, adversely affects the integrity and stability of the product. Bromelain is a natural mixture of protein-digesting enzymes derived from pineapple [17], It has a number of health-promoting properties, including immunomodulation and reducing of growth of certain microorganisms. In vitro studies have shown that bromelain has properties that reduce the growth of unfavourable bacteria which may contribute to changes in the mammary gland microbiota [18,19], Studies using pineapple extract have shown its effectiveness in inhibiting the growth of Staphylococcus aureus, a bacterium that causes mastitis, among other things. The authors of the study attribute the main role in reducing the growth of S. aureus to bromelain contained in the extract [20], Bromelain’s antibacterial mechanism is assumed to be related to its proteolytic properties. Bromelain induces enzymatic breakdown of proteins in bacterial cell membrane, which ultimately weakens the cell wall and leads to damage to the microbial cell.

Bromelain reduces the level of most inflammatory mediators and thus plays an important role as an anti-inflammatory agent. Studies conducted in mice have shown that bromelain induces an anti-inflammatory response by reducing synthesis of prostaglandin E2 (PGE-2) and cyclooxygenase-2 (COX-2), an enzyme involved in the synthesis of pro-inflammatory substances [17], In view of the anti-inflammatory effect of bromelain, studies have been conducted in cows with subclinical mastitis. The results showed that cows fed with bromelain, during periods of high ambient temperature maintained a lower number of somatic cells in milk compared to a control group [21], The increased number of somatic cells in milk may be associated with mastitis caused by bacteria.

In addition, bromelain has an anti-oedematous effect, consisting in increasing permeability of blood vessel walls, which allows an oedematous fluid from tissues re-enter vascular lumen, thus eliminating a problem of stasis [22],

In view of the above, it can be concluded that bromelain’s spectrum of action is broad and that it shows activity beyond the scope of action of synthetic NSAIDs and antibiotics, which are currently the main method of dealing with obstructed milk flow through the milk duct.

Accordingly, there is a long-standing but still unmet need to provide a solution for comprehensive support and improvement of lactation, particularly in conditions of obstructed milk flow and/or mastitis. Such a solution, unlike NSAIDs and antibiotics, must be safe both for mother and child, unlike home remedies, must be scientifically sound and - preferably - have additional nutritional benefits for mother and child and be of natural (otherwise non-synthetic) origin.

It is an object of the present invention to overcome the above problems of the prior art and to propose an alternative, safe, scientifically sound and optimized composition to support and improve lactation, particularly in conditions of obstructed milk flow and/or mastitis. This solution was unexpectedly achieved by a composition comprising a specially optimized form of lecithin in combination with bromelain. This composition further overcomes fundamental formulation and stability problems by combining, in a single dose, of soft-capsule incompatible bromelain and hard-capsule incompatible liquid lecithin.

The subject of the invention is an oral, lecithin-comprising composition for breastfeeding mothers, characterized in that it further comprises bromelain and that lecithin is deoiled.

Preferably, the composition of the invention is characterized in that deoiled lecithin and bromelain are present in a weight ratio of 8:1 to 4:1 , respectively, preferably 7:1 to 5:1 , most preferably 6:1.

Preferably, the composition of the invention is characterized in that deoiled lecithin is in a form of powder, granules, or a combination thereof.

Preferably, the composition of the invention is characterized in that deoiled lecithin comprises 65-75 wt% phospholipids.

Preferably, the composition of the invention is characterized in that deoiled lecithin is rapeseed lecithin.

Preferably, the composition of the invention is characterized in that bromelain is in a form of powder, granules, or a combination thereof.

Preferably, the composition of the invention is characterized in that bromelain has an enzymatic activity of at least 500 GDll/g ± 10%, preferably 2500 GDll/g ± 10%. Preferably, the composition of the invention is characterized in that it comprises at least one food- or pharmaceutically acceptable auxiliary substance, carrier or excipient.

Preferably, the composition according to the invention is characterized in that the auxiliary substance is an antioxidant and/or an anti-caking agent and/or a colour and/or a flavouring substance.

Preferably, the composition of the invention is characterized in that the anti-caking agent is a magnesium salt of a fatty acid, preferably magnesium stearate and/or silica.

Preferably, the composition of the invention is characterized in that it is in a solid form, especially powder, microbeads, granules, a capsule, a tablet, foodstuff or a food additive.

Preferably, the composition of the invention is characterized in that it is enclosed in a hard capsule, preferably made of a cellulose derivative, in particular HPMC.

Preferably, the composition according to the invention is characterized in that it contains 69 wt% deoiled lecithin, 11 wt% bromelain or a bromelain composition, 11 wt% magnesium stearate and 9 wt% silica.

The object of the invention is also use of the composition according to the invention to support and/or improve lactation, preferably in conditions of obstructed milk flow and/or mastitis.

Preferably, the use of the composition according to the invention is characterized in that the composition is used to increase the flowability and/or outflow of milk.

Preferably, the use of the composition according to the invention is characterized in that the composition is used to reduce concentration of inflammatory mediators in milk.

Preferably, the use of the composition according to the invention is characterized in that the composition is used at a daily dose corresponding to 2400 mg deoiled lecithin and 400 mg bromelain. Preferably, the use of the composition according to the invention is characterized in that the daily dose is divided into 6 equal doses, preferably in a form of 2 doses 3 times a day.

The present invention provides an oral composition for breastfeeding mothers comprising deoiled lecithin and bromelain, and the use of the composition according to the invention to support and/or improve lactation, preferably in conditions of obstructed milk flow and/or mastitis. The composition of the invention is a safe and non-pharmacological alternative to currently used medicines such as NSAIDs and antibiotics. At the same time, unlike traditional methods, the composition according to the invention is scientifically sound and allows the so- called standardization of the composition, i.e. ensuring a reproducible and verifiable content of the declared ingredients. Finally, the composition of the present invention allows for a comprehensive action in conditions of obstructed milk flow and/or mastitis. To date, disclosed medical recommendations and applied products from state of the art have not solved the above-mentioned technical problems, more particularly not simultaneously. Thus, the invention provides a solution to a long-perceived but hitherto unmet need.

Additionally, in preferred embodiments, the composition of the present invention comprises non-pharmacological ingredients of natural (non-synthetic) origin influencing the acceptability and availability of the composition of the present invention for breastfeeding mothers.

Subsequently, in preferred embodiments, specially optimized ingredients, in particular in terms of form and source (e.g., deoiled rapeseed lecithin), increase nutritional value and health-promoting properties compared to available solutions. By way of example, rapeseed lecithin has a more favourable fatty acid profile for better child development. This may have long-term epigenetic significance for their subsequent health and development. Moreover, in vivo studies indicate that rapeseed lecithin, in contrast to soybean lecithin, contributes to a greater diversity of bacteria in the gastrointestinal tract. In view of the above, the use of a particular rapeseed lecithin also has more benefits for both the child and the mother.

In addition, an additional advantage of using the compositions according to the invention is that the use of antibiotics is avoided, in the event of severe development of pathogenic microbiota in the milk ducts. Extensive use of antibiotics can lead to antibiotic resistance and, as a rule, is not recommended during breastfeeding.

The present invention also solves a hitherto unaddressed technical problem of combining in a single dose lecithin, which is difficult to enclose in a hard capsule, and bromelain, which digests soft capsules. This ensures a complex composition of two substances incompatible in terms of formulation and technology, which additionally has an advantage of increased stability and solving the problem of oils susceptible to UV light and oxidation. Thus, there is no requirement for special storage conditions or additional preservatives.

Finally, in the course of developing the compositions according to the invention, it unexpectedly became apparent that this particular combination of lecithin and bromelain, in suitable forms, from suitable sources, developed in a suitable form, makes it possible to achieve the recommended level of lecithin while reducing its dose. By way of example, the composition according to the invention, when used in the amount of 2400 mg a day, provides the same amount of phospholipids as 3600 mg of standard liquid lecithin. And it should be reiterated here that this is the lowest recommended amount. For the upper recommended limit (2 capsules comprising 1200 mg of liquid lecithin consumed 4 times a day), an amount of almost 9600 mg is required. For comparison, the equivalent of such a dose is 6400 mg of lecithin from the composition according to the invention. At the same time, it is still synergistically supported by bromelain enhancing its effects. Thus, despite the theoretical possibility, there is no need for using such high doses.

In conclusion, in order to achieve the same effect as the dose recommended in the literature, a lower dose of the composition according to the invention should be used and there is no need for an upper limit of the recommended intake. This has a direct effect on increasing the acceptability/compliance rate, firstly due to the reduction in the size of the dosage form (e.g. a smaller capsule), secondly, due to the reduction in the frequency of intake (e.g. 3 times a day instead of 4), and thirdly, due to the reduction in the total daily dose (e.g. 2400 mg instead of 3600 mg, or even 9600 mg, as recommended by the scientific literature and available products for recurrent milk duct plugging). A higher acceptability/compliance rate can also be indicated with respect to the use of conventional NSAIDs with antibiotics. Assuming the use of ibuprofen, antibiotic and lecithin in oil, according to the information available in the state of the art so far, a breastfeeding mother must take up to 9 dosage units per day: 3 antibiotic tablets, 1 probiotic capsule, 4 ibuprofen tablets and 1 gastroprotective capsule (e.g. omeprazole). The proposed dosage of the composition according to the invention is 6 capsules per day, mainly due to the desire to further reduce the size of a single dose from one larger capsule to two smaller ones, as a preferred variant of the invention.

The present invention also relates to the use of the composition according to the invention to support and/or improve lactation, preferably in conditions of obstructed milk flow and/or mastitis. Thus, the present invention will be applicable in breastfeeding mothers. Breastfeeding mothers, within the meaning of the present invention, are female mammals, especially women, in which the lactation process is partially or completely normal, irrespective of the frequency of breastfeeding of the child (and therefore also before birth and after cessation of breastfeeding).

Preferably, the composition of the invention is used to increase milk flowability and milk outflow. Equally preferably, the composition of the present invention is used to reduce the concentration of inflammatory mediators in milk. Both of the above applications improve the nutritional value and quality of milk and support milk production, without any therapeutic effect. This means that the composition of the present invention can be successfully used in both healthy and sick mothers.

As mentioned above, one of the unexpected effects of the composition according to the invention is its use in a preferably reduced daily dose corresponding to 2400 mg deoiled lecithin and 400 mg bromelain. Preferably, the daily dose is divided into 6 equal doses, preferably in the form of 2 doses 3 times a day (400 mg deoiled rapeseed lecithin and 66.67 mg bromelain composition each).

Example 1

Obtaining the compositions according to the invention

In a preferred embodiment, bromelain in the form of dried hygroscopic powder was obtained by liquefaction, removal of impurities, filtration and ultrafiltration followed by spray drying of pineapple stems and fruits. Bromelain is an enzyme that is found only in fresh pineapple fruits and young stems thereof. Furthermore, the raw material comprised a specified high enzymatic bromelain activity of 2500 GDll/g which influences the effectiveness of its action. This is a particularly advantageous embodiment due to the almost complete purity and high enzymatic activity of bromelain as compared to the currently available raw materials. Nevertheless, a batch with a lower enzymatic activity of 500 GDll/g was also prepared in order to investigate the range of the composition’s effectiveness. This value was achieved by supplementing bromelain with an inactive carrier (e.g., maltodextrin) to obtain the bromelain composition. A person skilled in the art can also achieve a similar effect by using other methods, without affecting the essence of the invention. As was subsequently demonstrated, even bromelain of 500 GDll/g ± 10% allows to achieve noticeable effects of supporting and improving lactation in combination with deoiled lecithin and does not affect the physicochemical parameters of the composition. One skilled in the art, without departing from the scope of the invention, will suitably select the enzymatic activity of bromelain, especially from at least 500 GDll/g ± 10%, and more preferably ± 10% of the 2500 GDll/g value, taking into account e.g. the efficacy to availability ratio. The bromelain was free of any contamination with other ingredients, as confirmed by a technical product test report.

In a preferred embodiment, lecithin, which was obtained by deoiling (removal of the mother oil using acetone) of liquid rapeseed lecithin derived from doubleimproved rapeseed varieties (erucic acid free, double-zero or 00). Rapeseed lecithin in the fatty acid profile has a higher content of polyunsaturated fatty acids (88%) in relation to soybean lecithin (74%) and a lower content of saturated acids (rapeseed -12%, soybean - 26%) [13], Rapeseed lecithin can contain from 3 to up to 5 times more monounsaturated oleic acid compared to soybean lecithin [13,23], Oleic acid, belonging to monounsaturated fatty acids (MLIFA), has properties that can be helpful in immunomodulation, treatment, as well as in prevention of various types of disorders such as cardiovascular diseases, autoimmune diseases or metabolic disorders [24], Rapeseed lecithin contains on average more phosphatidylcholine than soybean and sunflower lecithin and more phosphatidylethanolamine than soybean and sunflower lecithin [25], A composition comprising rapeseed lecithin is a particularly preferred embodiment of the invention. Nevertheless, without departing from the scope of the invention, a person skilled in the art will select, from a wide range of plant and animal lecithins, a lecithin of origin other than rapeseed, or combinations thereof. Indeed, one objective of the present invention is the safety and quality of the product. However, considering other parameters, e.g. availability and price, other sources of lecithin may be more advantageous.

Deoiling yielded rapeseed lecithin powder characterized by a higher phospholipid content (73 wt%) compared to traditional liquid lecithins. Deoiled rapeseed lecithin with a phospholipid content of 73 wt% has proven to be particularly advantageous due to its optimal properties. It is apparent to one skilled in the art that they can also select deoiled lecithins with a lower and higher phospholipid content. Without departing from the scope of the present invention, one skilled in the art will adjust the phospholipid % content, especially in the range of 65 - 75 wt.%, with respect to e.g. the efficacy to availability ratio. Rapeseed lecithin powder also contained carbohydrates - 8 wt%, glycolipids - 15 wt%; triglycerides - 3 wt% and water - 1 wt %. The phospholipid content in rapeseed lecithin powder was by approximately 52% higher compared to the average phospholipid content in liquid lecithins. The average phospholipid content in liquid lecithins is about 46 wt%, while the other components consist of carbohydrates - 5 wt%, glycolipids - 11 wt%, triglycerides - 37 wt% and water - 1 wt%. Therefore, in order to achieve the desired effect of using lecithin, it was reasonable to use 2400 mg of powdered lecithin per day instead of the suggested 3600 mg of liquid lecithin.

It is worth mentioning that forms of lecithin and bromelain other than powder are commercially available. Without departing from the scope of the invention, a person skilled in the art will select alternative forms of lecithin and bromelain, in particular granules, or a combination of powder and granules (e.g., in order to modify the release profile).

In a particularly preferred example of the invention, powdered bromelain (with an enzymatic activity of both 500 GDll/g and 2500 GDll/g) and lecithin were weighed in the weight ratios of 1 :6, respectively. A batch of compositions according to the invention with the weight ratios of bromelain and lecithin of 1 :4 and 1 :8, respectively, was also prepared. The ingredients of the composition were weighed on a special high-precision, high-sensitivity scale (RADWAG) and combined in a “V” type ribbon and rotary mixer until a homogeneous mixture was obtained.

Example 2

Bromelain and lecithin-comprising compositions according to the present invention in a solid form

A batch of hard capsules comprising the composition according to the preferred embodiment of Example 1 was prepared on the FlexaLab capsule filling machine. In a particularly preferred embodiment, the capsule is made of hydroxypropyl methylcellulose (HPMC) which, together with its substitutes, i.e. other cellulose derivatives, has the advantage of being of plant origin, acceptable for vegan and vegetarian consumption. Inside the capsule, as described in Example 1, was a composition according to the invention containing mother oil-free (deoiled) rapeseed lecithin in powder form, bromelain in powder form and auxiliary substances in the form of anti-caking agents: magnesium salts of fatty acids and silica.

In a particularly preferred embodiment, a single capsule contained 69 wt% deoiled rapeseed lecithin powder, 11 wt% bromelain powder composition, 11 wt% magnesium stearate, 9 wt% silica encapsulated in a hydroxypropyl methylcellulose (HPMC) capsule. The Applicant also prepared a trial batch of tablets, tableting the above composition on a single punch I KA laboratory tableting machine, as well as a trial batch of food gels containing the above composition, an antioxidant, a colour a flavouring substance, and a sweetener in an alginate-based carrier.

Without additional inventive work and without departing from the scope of the invention, one skilled in the art would propose other solid dosage forms, especially powder, microbeads, granules, tablets, foodstuff or a food additive.

In a preferred embodiment, at least one auxiliary substance, carrier, or excipient is food- or pharmaceutically acceptable, and all composition ingredients allow the ingestion thereof by vegans and vegetarians. As shown in Example 1 , the substances were weighed on a special high-precision, high-sensitivity scale (RADWAG) and combined in a “V” type ribbon and rotary mixer to obtain a homogeneous mixture.

Example 3

Use of the compositions of the present invention and dosage regimen determination

As lecithin was specially processed to obtain a higher concentration of phospholipids, as indicated in the first embodiment, in order to achieve the desired effect of using lecithin, it was reasonable to use the composition in the amount providing 2400 mg of lecithin powder per day, instead of the suggested 3600 mg of liquid lecithin.

The composition of the invention was used in breastfeeding mothers for the purpose of non-pharmacological support and improvement of lactation. In particular, it relates to the support and improvement of lactation, with particular benefit in conditions of obstructed milk flow and/or mastitis. In a preferred embodiment, the composition according to the invention is intended to reduce viscosity of milk, thereby increasing its flowability. This is due, among other things, to an increase in the amount of polyunsaturated fatty acids in breast milk, and thus a decrease in the viscosity thereof leading to an improvement in milk flowability and its increased outflow. This is particularly useful in conditions of obstructed milk flow and retention of larger quantities of milk caused by interruptions in breastfeeding. In another preferred embodiment, the composition of the present invention is intended to reduce the concentration of inflammatory mediators in milk, thereby improving the quality and value thereof. This is particularly useful in mastitis of the mammary gland, where there may be concerns about changes in milk quality caused by the infiltration of inflammatory mediators therein. This, in turn, is an undesirable phenomenon because of the nutritional value of milk and possible impact on the infant.

It should be emphasized that the above applications do not apply to pathological conditions requiring treatment, and the invention is only intended to support and improve the lactation process in order to increase the quality of milk and the comfort of the breastfeeding mother.

As a result of the formulation changes, aimed at making it possible to provide a composition combining bromelain, which is incompatible with soft capsules, and liquid lecithin, which is incompatible with hard capsules, it was unexpectedly found that the developed invention also allowed to reduce the amount of lecithin. Accordingly, the composition of the present invention also allows to reduce the unit dose and/or to reduce the dosage regimen compared to the solutions currently available in the state of the art. This has a direct impact on increasing the acceptability/compliance rate, firstly, due to the reduction in the size of the dosage form (e.g. a smaller capsule), secondly, due to the reduction in the frequency of intake (e.g. 3 times a day, instead of 4), thirdly, due to the reduction in the total daily dose (e.g. 2400 mg instead of 3600 mg, or even 9600 mg, as recommended by the scientific literature and available products for recurrent milk duct plugging).

In addition, the combination of specially optimized lecithin and bromelain allowed for their additionally beneficial, synergistic effect, because apart from reducing inflammatory mediators, bromelain also has proteolytic properties that can strengthen the flowability-enhancing and milk-flow-increasing effects of lecithin.

In view of the above, in a preferred embodiment, the composition of the present invention was used at a daily dose corresponding to 2400 mg of deoiled lecithin and 400 mg of bromelain. In an even more preferred embodiment, the above daily dose was divided into 6 equal doses (e.g. capsules), each containing 400 mg of deoiled rapeseed lecithin and 66.67 mg of the bromelain composition. In a particularly preferred embodiment, the composition of the invention was used in the form of 2 doses 3 times a day. It is recommended to consume the composition of the invention during a meal or as indicated by a physician/lactation specialist. 6 capsules contain a complex of 1750 mg of phospholipids from rapeseed lecithin powder (corresponding to the amount of phospholipids present in 3600 mg of standard liquid lecithin) and bromelain of 2500 GDll/g (GDU - gelatine digestion units). Similarly, a bromelain composition with an enzymatic activity of 500 GDll/g was used, resulting in noticeable effects of supporting and improving lactation when combined with deoiled lecithin and without changing the amount and frequency of the dosing above.

Example 4 Pilot study

In the pilot study, the follow-up group consisted of breastfeeding women aged 18- 45 years with breast milk flow disorders. Of the study group, 11 women had milk stasis, 9 had milk duct clogging, 5 had subacute mastitis, and two had non- infectious mastitis. On reporting to the health care professional, the disease condition had lasted for 2 days in 6 patients, for 3 days in another 6 patients, for 4 days in 2 patients, for 5 days in 1 patient and for 7 days in 3 patients. The followup lasted 15 days and consisted of four visits: one inpatient and three teleconsultations. The inpatient visit took place according to the lactation counselling standard. Subsequent visits in the form of a teleconsultation took place on days 3, 6-7 and between day 14 and 15 following the beginning of the study.

Patients received the following supplementation: 1 capsule containing L. salivarius SGL03 2 billion CFU and 200 mg inulin for 15 days and 3 x 2 capsules containing 1750 mg phospholipids from rapeseed lecithin powder and 2500 GDll/g bromelain for 5 days. If necessary, patients were additionally given NSAI Ds. Of the 20 women who qualified, 19 completed the follow-up and the results were statistically analysed. The primary endpoint of the study was the assessment of pain and the size of the area of increased breast cohesion (thickening). Pain sensation was assessed on a visual 10-point scale, where 0 meant no pain and 10 meant unbearable pain. The size of the area of increased breast cohesion was assessed by means of a visual scale indicating the % of the breast affected by the thickening. The secondary endpoints of the study were the number of women who were cured of the originally reported ailment, experienced improved milk flow from the breast, and continued breastfeeding.

All women experienced breast pain on the day of enrolment. The vast majority (n = 16) had impaired or no milk flow from the breast at baseline. During the followup, one woman was prescribed an antibiotic and 10 women used NSAI Ds. The average pain sensation on the day of enrolment in the group of patients who were receiving supplementation and NSAIDs was 6.4 on the VAS scale. After 3 days of the study, the average value was 3.8, after 6-7 days: 2.8 and at the end of the study (day 14 or 15): 1.9. The average pain sensation on the day of enrolment in the group of patients who received only supplementation throughout the follow-up period was 5.6. After 3 days of the study, the average pain value decreased to 3.8, after 6-7 days: to 1.6, and on the last day of the study (day 14 or 15): to 0.8. One woman had a pain level of 10 on the day of enrolment in the study. After 4 days of supplementation only, the pain decreased to level 2. In both groups, a highly significant (p < 0.01) reduction in pain was observed, with no significant differences found between the groups (p > 0.05) in this regard.

The above data prove that both supplementation in combination with NSAIDs, as well as on its own, has the effect of reducing the intensity of pain in the subsequent days of the follow-up. A slightly greater reduction in pain intensity on days 1-3 of the study occurred in the combination therapy group. In the case of exclusive use of supplementation, the subjects also experienced a significant improvement as regards pain sensation, with the greatest reduction occurring on days 6-7.

Improvement in the reduction of the size of the area of increased breast cohesion was observed, with very significant (p < 0.01) differences in the assessment of this parameter during the study. Increased breast cohesion in women, on the day of enrolment, affected on average 33% of the breast area, decreasing on each day of the follow-up to an average of 11% on the last day of the study.

Due to the intervention used, continued breastfeeding was maintained in 18 out of 19 women. Prompt and effective intervention reducing pain and further development of milk flow disorders can be crucial for the breastfeeding woman and her child. Based on the pilot study, it can be concluded that supplementation with bromelain, lecithin and a probiotic is effective in reducing breast pain in patients with selected conditions of milk flow disorders, both as a stand-alone intervention and in support of NSAID therapy (whenever the latter is necessary).

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Claims

1. An oral, lecithin-comprising composition for breastfeeding mothers, characterized in that it further comprises bromelain, and that lecithin is deoiled.

2. The composition according to claim 1, characterized in that deoiled lecithin and bromelain are present in a weight ratio of 8:1 to 4:1 , respectively, preferably 7:1 to 5: 1 , most preferably 6: 1.

3. The composition according to claim 1 or 2, characterized in that deoiled lecithin is in a form of powder, granules or a combination thereof.

4. The composition according to any one of the preceding claims, characterized in that deoiled lecithin comprises 65-75 wt% phospholipids.

5. The composition according to any one of the preceding claims, characterized in that deoiled lecithin is rapeseed lecithin.

6. The composition according to any one of the preceding claims, characterized in that bromelain is in a form of powder, granules, or a combination thereof.

7. The composition of any one of the preceding claims, characterized in that bromelain has an enzymatic activity of at least 500 GDll/g ± 10%, preferably 2500 GDU/g ± 10%.

8. The composition according to any one of the preceding claims, characterized in that it comprises at least one food- or pharmaceutically acceptable auxiliary substance, carrier or excipient.

9. The composition according to claim 8 characterized in that the auxiliary substance is an antioxidant and/or an anti-caking agent and/or a colourand/or a flavouring substance.

10. The composition according to claim 9 characterized in that the anti-caking agent is a magnesium salt of a fatty acid, preferably magnesium stearate and/or silica.

11. The composition according to any one of the preceding claims, characterized in that it is in a solid form, especially in the form of powder, microbeads, granules, a capsule, a tablet, foodstuff or a food additive.

12. The composition according to claim 11 , characterized in that it is enclosed in a hard capsule, preferably made of a cellulose derivative, in particular HPMC.

13. The composition according to claim 12, characterized in that it contains 69 wt% deoiled lecithin, preferably rapeseed lecithin, 11 wt% bromelain or a bromelain composition, 11 wt% magnesium stearate and 9 wt% silica.

14. The use of the composition according to any one of the preceding claims to support and/or improve lactation, preferably in conditions of obstructed milk flow and/or mastitis.

15. The use of the composition according to claim 14, characterized in that the composition is used to increase the flowability and/or outflow of milk.

16. The use of the composition according to claim 14 or 15, characterized in that the composition is used to reduce the concentration of inflammatory mediators in milk.

17. The use of the composition according to any one of claims 14 - 16, characterized in that the composition is used at a daily dose corresponding to 2400 mg of deoiled lecithin and 400 mg of bromelain.

18. The use of the composition according to claim 17, characterized in that the daily dose is divided into 6 equal doses, preferably in a form of 2 doses 3 times a day.