Sodium bicarbonate product for childbirth labor

Abstract

Use of an ingestible particle comprising sodium bicarbonate, wherein the particle has size in the range of more than 1.0 mm but not more than 5.0 mm, with a thickness in at least one dimension of more than 1.0 mm but not more than 2.0 mm; and wherein the particle contains more than 50 % (w / w) of the sodium bicarbonate, for preventing, alleviating or mitigating dystocic labor. The ingestible particles are comprised in a composition which is a suspension comprising the ingestible particles dispersed in an aqueous liquid, preferably a viscous aqueous medium.

Description

[0001] SODIUM BICARBONATE PRODUCT FOR CHILDBIRTH LABOR

[0002] Technical field of the invention

[0003] The present invention relates to the use of sodium bicarbonate compositions in preparation for childbirth labor. The sodium bicarbonate compositions are also useful for preventing, alleviating or mitigating dystocic labor. More specifically, the invention relates to improved dosage forms for sodium bicarbonate, which are useful for preventing, alleviating or mitigating dystocic labor. After ingestion, the compositions give rise to increased bicarbonate levels in the blood and a positive increase in extracellular fluid base excess, BE (Ecf), which contributes in preventing, alleviating or mitigating dystocic labor.

[0004] Background art

[0005] Sodium bicarbonate (NaHCOs) is a well-established nutritional ergogenic aid. Supplementation with sodium bicarbonate can improve high- intensity exercise performance by augmenting the body’s extracellular buffering capacity via an increase in bicarbonate concentration, with various analyses confirming its efficacy (Hadzic et al. The Impact of Sodium Bicarbonate on Performance in Response to Exercise Duration in Athletes: A Systematic Review. 2019. J Sports Sci Med 18: 271-281 ). Blood bicarbonate is part of the acid-base homeostatic bicarbonate buffer system, which is critical in regulating blood pH concentrations and supporting metabolic functions. As an extracellular buffering agent, NaHCOs enhances endogenous bicarbonate buffering capacity by inducing significant elevations in extracellular bicarbonate. Consequently, this enhances efflux of hydrogen cations (H+) from skeletal muscle, therefore delaying muscle fatigue and positively affecting numerous performance variables, such as power output and time to exhaustion.

[0006] Supplementation with sodium bicarbonate can be useful to prevent, alleviate or mitigate labor-induced acidosis, i.e. an imbalance in the body’s acid-base balance caused by the labor work. Labor-induced acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35.

[0007] Supplementation with sodium bicarbonate can also be useful to prevent, alleviate or mitigate labor-induced acidemia.

[0008] ’ Another benefit of sodium bicarbonate could be the improved recovery from labor work.

[0009] Substantial changes (~ 4-6 mmol / l) in blood bicarbonate improve the likelihood of performance-enhancing effects (Heibel et al. Time to optimize supplementation: modifying factors influencing the individual responses to extracellular buffering agents. 2018. Front Nutr 5: 35, de Oliveira et al. Extracellular Buffering Supplements to Improve Exercise Capacity and Performance: A Comprehensive Systematic Review and Meta-Analysis. 2022. Sports Med 52, 505-526). Consequently, large oral doses (0.2-0.3 g / kg body mass) are desirable to induce performance-enhancing elevations in the blood bicarbonate levels.

[0010] However, acute gastrointestinal (Gl) distress is a known side-effect of ingesting large amounts of NaHCOs (Burke & Pyne. 2007. Bicarbonate loading to enhance training and competitive performance. Int J Sports Physiol Perform 2: 93-97), particularly when administered as an aqueous solution (Carr et al. 2011 . Effect of sodium bicarbonate on [HCO3~], pH, and gastrointestinal symptoms. Int J Sport Nutr Exerc Metab 21 : 189-194],

[0011] A recent study [Middlebrook et al. 2021 . Capsule size alters the timing of metabolic alkalosis following sodium bicarbonate supplementation. Frontiers Nutr 8: 27] investigating the effects of NaHCOs supplementation using large (5.6 mm or larger) capsules reports some effects on acid-base responses but no effects on Gl symptoms and palatability.

[0012] Furthermore, Gl distress may deter individuals from using NaHCOs regardless of its potential ergogenic benefits (Heibel supra).

[0013] In conclusion, Gl distress such as nausea, vomiting and diarrhoea presents a major practical limitation for athletes’ use of NaHCOs.

[0014] It has been suggested that gastro-resistant capsules may alleviate symptoms that are typical with NaHCOs ingestion (de Oliveira et al. 2018. / s bypassing the stomach a means to optimize sodium bicarbonate supplementation? A case study with a post bariatric surgery individual. I nt J Sport Nutr Exerc Metab 26: 1-4). This was to some extent supported by Hilton et al. 2019. A novel ingestion strategy for sodium bicarbonate supplementation in a delayed-release form: a randomised crossover study in trained males. Sports Med 5: 4, who reported lower incidences of Gl symptoms, but also an unwanted delay in the time to peak blood [HCO3-] and pH.

[0015] In addition, enteric-coating has been suggested as a means to reduce gastric symptoms [Hilton et al. 2020. Enteric-Coated Sodium Bicarbonate Attenuates Gastrointestinal Side-Effects. Int J Sport Nutr Exerc Metab 30: 62-68], Results showed reduction in Gl symptoms, but failed to demonstrate the desired increase in blood [HCOs-] and pH.

[0016] Furthermore, efficient gastroresistant coatings, widely researched and used in pharmaceuticals, employ enteric polymers which are not regarded as natural ingredients or do not possess GRAS (generally regarded as safe) status by the regulatory bodies, and cannot thus be used for nutritional products like NaHCOs (Barbosa et al. 2017. Going natural: using polymers from nature for gastroresistant applications. Br J Pharm 2: 14-30],

[0017] US 2013 / 0236545 A1 discloses an oral pharmaceutical formulation which is useful for the treatment of cystinuria, when administered together with another formulation containing a Krebs cycle precursor salt. The formulation is a two-layered mini-tablet consisting of a core including at least bicarbonate salt and at least one prolonged-release matrix, and of a coating including at least one coating agent to ensure a prolonged release.

[0018] US 6,432,450 B1 and CN 109430669 A disclose effervescent compositions, i.e. compositions which are designed for releasing the bicarbonate salt within seconds in water prior to ingestion, thereby creating carbon dioxide already prior to ingestion.

[0019] RU 2550927 C2 discloses a cough medicament with granules containing sodium bicarbonate for reducing the viscosity of sputum. This implies that the sodium bicarbonate is released already in the oral cavity, again within seconds in water. Active labor during childbirth can, in many respects, be compared to exhausting exercise for a long period of time and with intermittent efforts. Labor dystocia remains one of the biggest dangers to women and newborns during labor. Labor dystocia, or dystocic labor, is clinically defined as slow or arrested progress of labor. The reason why labor progress is halted is still unknown.

[0020] During exertion, lactic acid is produced by glycolysis in all human cells. Glycolysis mainly occurs under hypoxic conditions, but the uterus is unique in its function and is glycolytic even under normoxic conditions. However, the production of lactate is lower when oxygen is available. For labor to proceed and end successfully, the uterus needs to produce strong, coordinated, effective contractions. During the regular pattern of labor contractions, uterine blood circulation is reduced with every contraction, and metabolism briefly becomes anaerobic. When the contraction subsides, lactate and other metabolites associated with hypoxia are expelled, and new, oxygenated blood is transported to the muscle. This process leads to an average level of lactate in the tissue and good labor progress [Wray S. Insights into the uterus. Exp Physiol. 2007;92(4):621-631 .]. Recent research has shown that the uterus needs these periods of hypoxia to trigger the next contraction [Wray S, Carvajal J. Introduction: myometrial physiology-time to translate? Exp Physiol. 2014;99(3):487-488],

[0021] Conversely, during dystocic labor, lactate removal appears to deteriorate, and lactate and other metabolites accumulate in the tissue. This is accompanied by an acidification of the uterine muscle.

[0022] Acidification inhibits the Ca2+channels in the myometrial cells and leads to a decreased inflow of Ca2+into the muscle cells. This makes the labor contractions weaker and and consequently less active [Wray S, Carvajal J. Introduction: myometrial physiology-time to translate? Exp Physiol. 2014;99(3):487-488.].

[0023] It seems essential for the uterus to emit lactate in the event of overproduction during hypoxia and to withdraw lactate back into the tissue, if necessary, as a form of energy [Akerud H, Ronquist G, Wiberg-ltzel E. Wiberg-ltzel E. Lactate distribution in culture medium of human myometrialbiopsies incubated under different conditions. Am J Physiol Endocrinol Metab. 2009;297(6):E1414-9.]. Amniotic fluid appears to be a reservoir for lactate produced by the feto-maternal unit.

[0024] High levels of amniotic fluid lactate (AFL) (> 10.1 mmol / L) are overrepresented in dystocic deliveries compared to deliveries with normal progress, where low levels of AFL (<10.1 mmol / L) are more common [Wiberg- Itzel E, Pettersson H, Andolf E, et al. Lactate concentration in amniotic fluid: a good predictor of labor outcome. Eur J Obstet Gynecol Reprod Biol. 2010;152(1 ):34-38.].

[0025] Since the 1970s, it has been known that amniotic fluid contains a high concentration of lactate. Wiberg-ltzel E, Akerud H, Andolf E, et al. Association between adverse neonatal outcome and lactate concentration in amniotic fluid. Obstet Gynecol. 2011 ; 118(1 ): 135-142. showed that in a group with an AFL > 10.1 mmol / L significantly more neonates had an adverse neonatal outcome. This was accompanied by a pH < 7.05 and base deficit > 12 in the umbilical artery.

[0026] A randomized controlled trial studied whether oral intake of bicarbonate can stimulate and enhance the outcome of dystocic deliveries with high AFL levels (> 10.1 mmol / L) [Wiberg-ltzel E, Wray S, Akerud H. A randomized controlled trial of a new treatment for labor dystocia. J Matern Fetal Neonatal Med. 2018;31 (17):2237-2244], The study results show that AFL levels fell significantly in the group that was adminestered bicarbonate orally compared to the untreated group. The study also showed that those with high AFL levels benefited most from bicarbonate. The frequency of spontaneous vaginal deliveries was substantially higher in the bicarbonate treated group, and a difference in fetal outcome was shown between the two groups. The pH in maternal blood was increased significantly in the bicarbonate treated. Subjects in the treated group were given 4.26 g of sodium bicarbonate dissolved in water. It is desirable to give higher doses of bicarbonate to maintain an even higher blood pH avoiding acidosis, i.e. a pH lower than 7.35. However as discussed above, high doses of oral bicarbonate in water is known to cause gastrointestinal distress. Seyedi et al., J Obstet Gynaecol Res. 2021 ; 47(1 ): 114-118 discloses a trial investigating the effect of oral sodium bicarbonate solution on delivery outcome of primiparous women with labor stagnation.

[0027] Musaba et al., PLoS ONE. 2021 ; 16(2): e0245989 discloses a trial investigating the effect of bicarbonate solution infusion on maternal and perinatal outcomes among women with obstructed labor.

[0028] Wray et al., "Pharmacological Interventions in Labor and Delivery", Annu. Rev. Pharmacol. Toxicol. 2023. 63:471-489, summarizes the drugs available to help women during the different stages of labor and induction of labor, also highlighting the usefulness of sodium bicarbonate.

[0029] Accordingly, there is a need for compositions and methods for intake of sodium bicarbonate, NaHCOs, which are associated with a significant reduction in Gl side effects following intake, for use in preventing, alleviating or mitigating dystocic labor.

[0030] Summary of the invention

[0031] It is an object of the present invention to provide compositions and methods for intake of sodium bicarbonate, NaHCOs, which are associated with a significant reduction in Gl side effects following intake for use in preventing, alleviating or mitigating dystocic labor.

[0032] It is a further object to provide compositions and methods for intake of sodium bicarbonate, which facilitate the intake of sufficient amounts of sodium bicarbonate to prevent, alleviate or mitigate dystocic labor.

[0033] It is a further object to provide compositions and methods for intake of sodium bicarbonate by a pregnant woman as a preparation for childbirth labor.

[0034] It is also an object to provide compositions and methods for decreasing the risk of an adverse neonatal outcome, which in turn is associated with increased costs etc.

[0035] For these and other objects which will be evident from this disclosure, the present invention provides according to a first aspect a composition which is a suspension comprising ingestible particles dispersed in a viscous aqueous medium, for use in preventing, alleviating or mitigating dystocic labor.

[0036] The viscosity of the aqueous medium prevents or delays sedimentation of the ingestible particles when dispersed in the viscous aqueous medium until the dispersion has been ingested.

[0037] The ingestible particle is comprising sodium bicarbonate, wherein the particle has size in the range of more than 1 .0 mm but not more than 5.0 mm, with a thickness in at least one dimension of more than 1 .0 mm but not more than 2.0 mm; and wherein the particle contains more than 50 % (w / w) of the sodium bicarbonate.

[0038] The inventors have realized and demonstrated that ingestible particles with these dimensions achieve an efficient uptake of sodium bicarbonate, NaHCOs, but with a low occurrence of Gl side effects. The particles facilitate ingestion and uptake of sodium bicarbonate salt in amounts in the range of 0.20 - 0.30 g sodium bicarbonate salt per kg of body weight or higher, which is necessary to achieve a substantial change (~ 4-6 mmol / l) in blood bicarbonate that improves the likelihood of performance-enhancing effects. This also implies that the particles facilitate ingestion and uptake of sodium bicarbonate salt in amounts, such as in the range of 0.20 - 0.30 g sodium bicarbonate salt per kg of body weight or higher, which is associated with efficient labor work and a successful vaginal delivery.

[0039] The inventors have realized and demonstrated that the ingestible particles achieve an efficient uptake of sodium bicarbonate, but with a low occurrence of Gl side effects, in particular when dispersed in a viscous medium, such as a gel or a fluid with viscoelastic properties or a viscous liquid.

[0040] According to a second aspect, there is provided a kit for preparing a sodium bicarbonate composition, the kit comprising ingestible particles as defined herein; and an aqueous medium as defined herein, for use in preventing, alleviating or mitigating dystocic labor.

[0041] According to a further aspect, there is provided a kit for preparing a sodium bicarbonate composition, the kit comprising ingestible particles as defined herein; dry components of the aqueous medium as defined herein; and optionally water, for use in preventing, alleviating or mitigating dystocic labor.

[0042] According to a further aspect, there is provided a method for preparing a pregnant woman for labor, comprising the step of ingesting the sodium carbonate composition comprising the ingestible particles.

[0043] According to one further aspect, the composition comprising the ingestible particles and the kit are useful to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia. There is provided a method to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia in a in a pregnant woman, comprising the step of ingesting the composition comprising the ingestible particles.

[0044] According to one further aspect, the ingestible particles are useful in the composition to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia in a pregnant woman.

[0045] According to a further aspect, the composition comprising the ingestible particles and the kit are furthermore useful to treat dystocic labor in a pregnant female subject. This implies that the composition is a pharmaceutical composition. There is provided a method of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the composition comprising the ingestible particles. The composition and the kit are useful in a method of treating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the composition comprising the ingestible particles.

[0046] According to a further aspect, the ingestible particles are furthermore useful to treat dystocic labor in a pregnant female subject. There is provided a method of treating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the ingestible particles. The ingestible particles are useful in a method of treating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the ingestible particles. Preferred embodiments and further aspects are defined in the appended claims, listed embodiments and throughout the application text.

[0047] Brief description of the drawings

[0048] Fig. 1 shows plasma standard bicarbonate concentrations measured before and after ingestion of sodium bicarbonate particles.

[0049] Fig. 2 shows plasma standard bicarbonate concentrations and extracellular fluid base excess levels measured before and after ingestion of sodium bicarbonate particles.

[0050] Fig. 3 shows uptake of bicarbonate from the sodium bicarbonate particles in combination with either a high-viscosity vehicle or a vehicle of lower viscosity.

[0051] Fig. 4 shows blood plasma bicarbonate levels measured after intake of sodium bicarbonate particles.

[0052] Fig. 5 compares progress of the dissolution of sodium bicarbonate in the form of granulate, 0.5-1 .0 mm, with the form of minitablets, 1 .5 x 3.0 mm.

[0053] Fig. 6 shows release of NaHCOs from minitablets over time when dispersed in different vehicles and under different conditions.

[0054] Fig. 7 compares viscosity and shear-thinning properties of two vehicles.

[0055] Fig. 8 shows an oscillatory test for a viscoelastic medium.

[0056] Fig. 9 shows effects of blood pH and plasma bicarbonate concentration for an athlete ingesting the inventive nutritional supplement composition.

[0057] Fig. 10 shows effects on plasma bicarbonate concentration and extracellular base excess levels for a female athlete ingesting the inventive nutritional supplement composition.

[0058] Detailed description

[0059] The composition provided herein is a suspension comprising ingestible particles dispersed in a viscous aqueous medium.

[0060] The ingestible particles comprise sodium bicarbonate and have a well- defined size. The ingestible particles are particles are useful per se in compositions to prepare a pregnant woman for labor in connection with vaginal delivery. Intake of NaHCOs particles according to the invention can be demonstrated to reduce the gastrointestinal side effects seen following intake of a comparable amount of NaHCOs in solution or in capsules.

[0061] Needless to say, the ingestible particles are designed for releasing the sodium bicarbonate in the body, and more specifically for releasing the sodium bicarbonate in the small intestine. The ingestible particles are designed for releasing the sodium bicarbonate prior to the large intestine.

[0062] The ingestible particle is comprising sodium bicarbonate salt, wherein the particle has a size in the range of more than 1 .0 mm and not more than 5.0 mm, such as not more than 4.0 mm, with a thickness in at least one dimension of more than 1 .0 mm but not more than 2.5 mm, such as not more than 2.0 mm, such as not more than 1.8 mm; and wherein the particle contains more than 50 % (w / w) of the sodium bicarbonate. The ingestible particle typically has a size in the range of 1 .2 -5.0 mm, with a thickness in at least one dimension of 1 .2 - 2.0 mm.

[0063] Being smaller than 2.0 mm in at least one dimension provides a good palatability and at the same time allows the ingestible particles to freely pass the pyloric sphincter and therefore has a short gastric transit time which is beneficial. This results in a low level of dissolution of NaHCOs in the gastric chamber, significantly reducing potential upper Gl distress. The terms “dissolution” and “release” are used interchangeably in this document.

[0064] The ingestible particles do not disintegrate; instead the sodium bicarbonate dissolves or erodes successively from the particle surface over time. This is firstly reducing potential upper Gl distress, but secondly - equally important - provides a prolonged duration of the desired increase in blood [HCO3-] and pH.

[0065] The mechanism for uptake of sodium bicarbonate in the intestine goes via the active uptake of sodium, which involves Na+ / H+exchange. The protons thus secreted into the intestine will neutralize the bicarbonate which forms carbonic acid which, in turn, forms water and CO2. The last step is catalyzed by carboanhydrase in the luminal wall of the small intestine. The dissolved CO2 will readily diffuse through cell membranes and enter the blood stream. There is no scientific evidence for transport of bicarbonate ions as such over cell membranes being of any importance.

[0066] The net effect of these processes will be an increase in pH and bicarbonate levels in blood, including fetal blood, and interstitial liquid

[0067] The ingestible particles and the compositions comprising the ingestible particles can be supplied to the pregnant woman who ingests them as part of her preparations for childbirth and labor in connection with vaginal delivery. The ingestible particles and the compositions comprising the ingestible particles can be supplied to the pregnant woman when the onset of labor has been determined to have occurred. The ingestible particles and the compositions can also be administered to the woman in a clinical setting. The ingestible particles and the compositions can be supplied as part of a general program to all pregnant women who wish to prepare themselves for the endurance associated with labor work and giving birth. They can also be supplied to pregnant women who are at higher risk of facing a difficult childbirth and associated labor work, e.g. primiparous women or multiparous women who have previously experienced a childbirth with complications or an extended childbirth, e.g. for more than 10-12 hours from the onset of labor.

[0068] In the present disclosure, the onset of labor is considered to be when at least one of the following criteria are fulfilled:

[0069] - Regular uterine contractions at least every six minutes with evidence of change in cervical dilation or cervical effacement between consecutive digital examinations.

[0070] - Regular contractions occurring less than 10 minutes apart and progressive cervical dilation or cervical effacement.

[0071] - At least three painful regular uterine contractions during a 10-minute period, each lasting more than 45 seconds.

[0072] The ingestible particles and the compositions comprising the ingestible particles can be supplied to a pregnant woman prior to administration of oxytocin or oxytocin analogs. They can also be supplied to a pregnant woman who has been diagnosed with labor dystocia. If labor dystocia is confirmed, oxytocin or oxytocin analogs are suggested for augmentation. In particular, the ingestible particles and the compositions can be supplied to a pregnant woman who has been diagnosed with labor dystocia prior to administration of oxytocin or oxytocin analogs.

[0073] As used herein, oxytocin analogs refer to drugs which are indicated for labor augmentation. Oxytocin analogs may be structurally similar to oxytocin.

[0074] Without wishing to be limited to any particular theory, it is considered that the combination of the ingestible particles and oxytocin is particularly useful. Studies show that the dystocic myometrium is in an exhausted state. There is a local acidemia and increased lactate levels caused by the uterine contractions and repeated transient hypoxic episodes. The buildup of acid is believed to impede calcium entry into the myocytes, and thus the myometrium is unable to produce strong contractions and labor stalls. Under these conditions, oxytocin does not effectively stimulate contractions. The ingestible particles and the compositions comprising the ingestible particles can prevent or mitigate the local acidemia, thereby potentiating the effect of coadministered oxytocin.

[0075] The ingestible particles and the compositions comprising the ingestible particles can also be supplied to women in labor who exhibit levels of amniotic fluid lactate (AFL) which are associated with dystocic deliveries, e.g. > 10.1 mmol / L. In one embodiment, the AFL level is measured and the ingestible particles are provided to women who have levels of amniotic fluid lactate (AFL) which are associated with dystocic deliveries, e.g. > 10.1 mmol / L.

[0076] The ingestible particles and the compositions comprising the ingestible particles are advantageously supplied to the pregnant woman well in advance of the onset of labor. Thus, the ingestible particles and the compositions comprising the ingestible particles are advantageously supplied to the pregnant woman when uterine contractions have begun, but before they have matured into the more regular uterine contractions which are characteristic for the onset of labor. The ingestible particles and the compositions can also be supplied after the onset of labor. They can also be supplied multiple times before or during labor as needed, especially if the labor work is extended over time and / or in the case of multiple births. It is estimated that a buffering effect of the ingestible particles occurs within approximately 30-60 min after ingestions, and that the best buffering effect occurs within approximately 90- 120 min after ingestions. The buffering effect decreases slowly over time, and a further serving of the ingestible particles can be supplied within 5-10 hours if needed.

[0077] The ingestible particles and the compositions comprising the ingestible particles are advantageously supplied to the pregnant woman at the same time as or prior to administering oxytocin or oxytocin analogs, preferably 30 min - 5 hours prior to supplying oxytocin or oxytocin analogs. They can also be supplied to the pregnant woman after oxytocin or oxytocin analogs have been administered.

[0078] By time, bicarbonate will be distributed further to other compartments in the body. Bicarbonate will be eliminated by renal secretion so that most of the alkalizing effect of bicarbonate will have disappeared within 24-36 h.

[0079] Neutralization of bicarbonate in the stomach and in the small intestine are equivalent in terms of alkalizing effect on the human body. While excessive exposure to bicarbonate in the stomach should be avoided, some degree of exposure is believed to be possible while still achieving high Gl tolerability.

[0080] Partial, but limited, release of sodium bicarbonate will occur in the stomach. Part of the sodium bicarbonate thus dissolved will react with gastric acid to produce carbonic acid / carbon dioxide, while the main part of it will be transported into the small intestine.

[0081] Preferably, substantially all sodium bicarbonate in the particles is fully dissolved and available for uptake into the blood before leaving the small intestine. This prevents release of sodium bicarbonate in the large intestine and reduces potential lower Gl distress.

[0082] Accordingly, the ingestible particles can be used in a composition given to women preparing for childbirth labor, without the risk of severe Gl distress as observed with other types NaHCOs formulations.

[0083] It is preferred that the ingestible particle is comprising more than 65 % (w / w) of the sodium bicarbonate, such as more than 75 % (w / w), such as more than or equal to 80% (w / w) of the sodium bicarbonate. It is also preferred that the ingestible particle is comprising less than 90 % (w / w) of the sodium bicarbonate, such as less than or equal to 85 % (w / w) of the sodium bicarbonate.

[0084] Preferably, each ingestible particle comprises less than 80 mg sodium bicarbonate, such as less than 50 mg, preferably less than 30 mg, more preferably less than 20 mg sodium bicarbonate. Further preferably, each ingestible particle comprises more than 5 mg sodium bicarbonate, such as more than 10 mg, preferably more than 15 mg sodium bicarbonate. Typically, each tablet is comprising 5-30 mg, e.g. 10-20 mg, such as 15-20 mg sodium bicarbonate.

[0085] The ingestible particle has a thickness in at least one dimension of

[0086] < 2.5 mm, such as < 2.0 mm. It is demonstrated herein that athletes consider that particles having a thickness of less than or equal to 2.0 mm, e.g. 1.5 mm, are considerably easier to swallow than particles with a thickness larger than 2.0 mm, e.g. 2.3 mm. The palatability may be further improved by combining the particles with a viscous fluid which is ingested. It is furthermore considered that a thickness of less than or equal to 2.5 mm, such as less than or equal to 2.0 mm allows the particles to rather freely leave the stomach through the pyloric sphincter, and therefore decreases the risk for Gl distress in the stomach.

[0087] The ingestible particle preferably has a thickness in at least one dimension of < 1.8 mm, such as < 1 .6 mm, preferably < 1 .5 mm. These dimensions ensure a good palatability and at the same time allows the ingestible particles to freely pass the pyloric sphincter and therefore has a short gastric transit time which is beneficial. This results in a low level of dissolution of NaHCOs in the gastric chamber, significantly reducing potential Gl distress.

[0088] The ingestible particle could have a thickness in at least one dimension of > 1 .0 mm, preferably > 1 .2 mm, e.g. > 1 .5 mm. It has been demonstrated that thinner particles (< 0.5 mm) are associated with a faster dissolution time in the gastric chamber, which may in turn cause Gl distress. It is also demonstrated herein that particles having a size of 0.5 - 1 .0 mm are associated with moderate Gl symptoms. The lower limit for the thickness ensures that the extent of dissolution in the mouth is minimal and the rate of release in the stomach is adequately attenuated, without any need for an enteric coating. The ingestible particle, e.g. the tablets or mini tablet, is preferably non-layered. This implies that the particle is essentially homogenous and that it does not contain any coating. The particle is thus not multi-layered. Preferably, the ingestible particle is a non-layered, uncoated tablet. This is useful to ensure efficient release of the sodium bicarbonate salt in the small intestine, which means that the bicarbonate content is available for uptake into the blood. Typically, the sodium bicarbonate content in the ingestible particle is fully dissolved within less than 3 h after ingestion, preferably less than 2 h after ingestion. A slower dissolution, e.g. more than 4 hours, leads to release of sodium bicarbonate in the large intestine, which in turn is associated with undesirable lower Gl symptoms, such as diarrhea.

[0089] The ingestible particle preferably has a size of < 4.0 mm, such as < 3.5 mm, such as < 3.0 mm, such as < 2.0 mm, or even < 1 .8 mm or < 1 .6 mm. Suitable particle sizes are e.g. 1 .2 - 4.0 mm, e.g. 1 .2 - 3.0 mm, e.g. 1 .2 - 2.0 mm or 1.2 - 1.8 mm. These dimensions ensure a good palatability with a sufficient intake of bicarbonates. Larger particle sizes than 5.0 mm, such as large capsules, are more difficult to ingest, especially for a performing athlete.

[0090] It is preferred that the ingestible particle is spheroid shaped. Typically, the ingestible particle can have a curvature where the side height is less than the overall thickness. Preferred formats for the ingestible particles include pellets, beads, tablets and granules. A particularly preferred format is a tablet, or a mini tablet.

[0091] In certain embodiments, the somewhat spheroid particles have a diameter / thickness ratio of 3:2 to 3: 1 , or 1 :3 to 2:3.

[0092] In one embodiment, the ingestible particle is a tablet or a mini tablet with a thickness of more than 1.0 mm but not more than 2.0 mm and a diameter of more than 1 .0 mm but not more than 5.0 mm, such as a thickness of 1.2 - 2.0 mm and a diameter of 1 .2 - 5.0 mm. The tablet preferably has a thickness of < 1 .8 mm, such as < 1 .6 mm, preferably < 1 .5 mm. These dimensions ensure a good palatability and at the same time allows the tablets to freely pass the pyloric sphincter and therefore has a short gastric transit time which is beneficial. This results in a low level of dissolution of NaHCOs in the gastric chamber, significantly reducing potential Gl distress. The tablet could have a thickness of > 1 .0 mm, most preferably > 1 .2 mm. It is demonstrated herein that thinner particles (< 0.5 mm) are associated with a faster dissolution time in the gastric chamber, which may in turn cause Gl distress. It is also demonstrated herein that particles having a size of 0.5 - 1 .0 mm are associated with moderate Gl symptoms. The tablet preferably has a diameter of < 4.0 mm, such as < 3.5 mm, such as < 3.0 mm, such as < 2.0 mm, or even < 1 .8 mm or < 1 .6 mm. Suitable tablet diameters are e.g. 1 .2 - 4.0 mm, e.g. 1 .2 - 3.0 mm, e.g. 1 .2 - 2.0 mm or 1.2 - 1 .8 mm. These dimensions ensure a good palatability with a sufficient intake of sodium bicarbonate. Larger tablet sizes than 5.0 mm are more difficult to ingest, especially for a performing athlete.

[0093] It is preferred that the particles, e.g. the tablets or mini tablets, are nondisintegrating. Since the ingestible particles do not disintegrate, the sodium bicarbonate dissolves or erodes successively from the particle surface over time. This reduces potential Gl distress and provides a prolonged duration of the desired increase in blood [HCOs’] and pH.

[0094] The ingestible particle is not dissolved to any large degree in the mouth or in the stomach. This reduces potential Gl distress. Since the particle is present for a considerably longer time in the stomach, more sodium bicarbonate is released in the stomach than in the mouth. A suitably delayed release of sodium bicarbonate from the ingestible particle can advantageously be achieved by incorporating the ingestible particles in a viscous vehicle, such as a gel or other viscoelastic medium.

[0095] The sodium bicarbonate content in the ingestible particle is fully dissolved before leaving the small intestine, which means that the sodium bicarbonate content is available for uptake into the blood. Typically, the sodium bicarbonate content in the ingestible particle is fully dissolved within less than 3 h after ingestion, preferably less than 2 h after ingestion. As demonstrated in the examples, this is advantageous compared to e.g. larger capsules as it ensures that the sodium bicarbonate is available for uptake into the blood. Preferably, the time to reach 90 % (T90% max) of maximum blood plasma bicarbonate concentration after ingestion of the ingestible particle is less than 3 h after ingestion. A slower dissolution and associated higher T90% max, e.g. more than 4 hours, leads to release of sodium bicarbonate in the large intestine, which in turn is associated with undesirable lower Gl symptoms, such as diarrhea. It is preferred that the ingestible particle does not have any enteric coating as this delays the dissolution and associated T90% max. It is thus preferred that the ingestible particle does not have any coating.

[0096] In addition to the sodium bicarbonate salt, the ingestible particle may comprise excipients, summing up to 100 % (w / w) together with the sodium bicarbonate salt. The ingestible particle may thus further comprise at least one of a binder, a lubricant and a glidant. The ingestible particles may also comprise further excipients.

[0097] In certain embodiments, the ingestible particle is further comprising a binder, typically in an amount of 1-50 % (w / w), e.g. 1-30 % (w / w) or 1-15 % (w / w). The binder component is selected to fulfil the requirement on gradual release of sodium bicarbonate by erosion of the particle as described above. A preferred binder is selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropyl cellulose (HPC) and polysaccharides, and combinations thereof. Further preferred binders are microcrystalline cellulose and gelatin which can also in the combinations as set out above. Preferred polysaccharide binders are selected from high molecular weight alginates, pectins, gum tragacanth and gum acacia, and combinations thereof, such as. high molecular weight alginates, pectins and gum acacia, and combinations thereof. In certain embodiments, the binder is selected from calcium carbonate and gum acacia, and combinations thereof. In one preferred embodiment, the binder contains HPC. HPC provides a good mechanical stability to the particle. In certain preferred embodiments, the binder is HPC; such as in an amount of 1-30 % (w / w), 1-15 % (w / w) or 5-15% (w / w) of the ingestible particle. In certain embodiments, the binder is selected from HPC and gum acacia, and combinations thereof.

[0098] In certain embodiments, the ingestible particle is further comprising a lubricant, typically in an amount of 0.1-10 % (w / w), e.g. 1-5 % (w / w). A preferred lubricant is selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof. In certain embodiments, the lubricant is magnesium stearate.

[0099] In certain embodiments, the ingestible particle is further comprising a glidant, typically in an amount of 0.1-5 % (w / w), e.g. 1-3 % (w / w). A preferred glidant is fumed silica (anhydrous colloidal silica).

[0100] In certain embodiments, the ingestible particle is further comprising further excipients selected from sugars and complex carbohydrates, typically in an amount of 1-50 % (w / w), e.g. 1-40 % (w / w), e.g. 1-30 % (w / w) e.g. 1-20 % (w / w), e.g. 1-10 % (w / w). Preferred sugars are selected from glucose, fructose, sucrose and isomaltulose, typically in an amount of 1-50 % (w / w), e.g. 1-40 % (w / w), e.g. 1-30 % (w / w), e.g. 1-20 % (w / w), e.g. 1-10 % (w / w). Preferred complex carbohydrates are selected from maltodextrin, dried glucose syrup and dried fructose syrup, typically in an amount of 1-50 % (w / w), e.g. 1-40 % (w / w), e.g. 1-30 % (w / w), e.g. 1-20 % (w / w), e.g. 1-10 % (w / w).

[0101] The ingestible particles could preferably have one of the following compositions (summing up to 100 wt%):

[0102] (A) Sodium bicarbonate 75 - 85 wt %; Calcium carbonate 5 - 10 wt %; Hydroxypropyl cellulose 5 - 10 wt %; Maltodextrin 0.1 - 1.0 wt %; Gum acacia 1 - 3 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0103] (B) Sodium bicarbonate 82 - 92 wt %; Hydroxypropyl cellulose 5 - 15 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1.0 %.

[0104] (C) Sodium bicarbonate 80 - 90 wt %; Calcium phosphate 5- 15 wt %; Gum acacia 1 - 5 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0105] Preferably, the compositions are formulated as minitablets with a diameter within the range of 1 .2 - 5.0 mm and a thickness within the range of 1.2 - 2.0 mm.

[0106] The composition is a suspension comprising the ingestible particles dispersed in an aqueous medium. The ingestible particles are preferably suspended in the aqueous medium to facilitate intake and to improve palatability. The aqueous medium may e.g. be a viscous solution or a colloidal suspension. Preferably, the dry components of the aqueous medium are first mixed with water to obtain the aqueous medium, followed by addition of the particles. The aqueous medium should preferably be transparent with a thick consistency that can be spooned directly from the vessel used.

[0107] The composition can thus be prepared by a method involving suspending the ingestible particles in the aqueous medium. In an optional preceding method step, the aqueous medium is prepared by mixing dry components of the aqueous medium with water.

[0108] The ingestible particles shall preferably be freshly dispersed in the aqueous medium shortly before ingestion so as to prevent undesired dissolution of the sodium bicarbonate prior to ingestion. The resulting suspension shall preferably be ingested within 15 minutes, such as within 5 minutes, after preparation. The released amount of sodium bicarbonate shall be as low as possible prior to ingestion, preferably less than 20 % of the total amount ingested, such as less than 15% of the total amount ingested.

[0109] It is preferred that the aqueous medium is a viscous aqueous medium, such as a viscous aqueous liquid, such as a viscous aqueous solution, to facilitate intake and to improve palatability. Preferably, the viscous aqueous medium is a viscoelastic medium. A preferred viscoelastic medium is a gel. The viscous aqueous medium may also be a viscous liquid. Since sodium bicarbonate has a high density, the ingestible particles containing high amounts, up to 85% or even higher, thereof will also have a high density. If these particles are dispersed in water, they will rapidly sink to the bottom of the vessel. The viscosity of the medium should be high enough to prevent sedimentation of the ingestible particles when dispersed in the viscous medium until the dispersion has been ingested. It is preferred that the sedimentation rate of a single ingestible particle in the unstirred viscous aqueous medium is less than 70 mm / min, such as less than 20 mm / min, such as less than 10 mm / min. The sedimentation rate of minitablets in a medium of intermediate viscosity, as in Example 2, is approximately 60 mm / min, c.f. Example 8. It is particularly preferred that the sedimentation rate of a single ingestible particle in the unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min. The sedimentation rate of minitablets in a viscous medium, as in Example 1 , is less than 0.5 mm / min, c.f. Example 8. It is also demonstrated herein (Figure 3) that using a vehicle with high viscosity achieves a faster uptake of sodium bicarbonate during the first 90 min after intake, possibly due to faster gastric emptying of the particles. In addition, a viscous vehicle improves the palatability of the composition and ensures that the particles are readily ingested and do not remain in the vessel. A further advantage of a viscous vehicle is that it slows down mixing of the vehicle, e.g. when ingested, and thereby decreases the rate of erosion for the tablets in the composition.

[0110] Without wishing to be limited to any particular theory, it is envisaged that the viscous medium protects the particles from direct exposure to the highly acidic environment of the stomach wall, where hydrochloric acid is excreted. It is considered that this may protect the integrity of the particles and is believed to prevent or decrease gastrointestinal problems which could otherwise occur.

[0111] The interactive combination of the ingestible sodium bicarbonate particles and the viscous aqueous medium in the present composition prevents acidosis, including exercise-induced acidosis, in a surprisingly efficient manner: The size of the ingestible particles allows both for a facilitated intake with improved palatability and a significant reduction in Gl side effects. The viscous aqueous medium not only facilitates intake of sufficient amounts of sodium bicarbonate by keeping the particles dispersed in the medium, but also delays the release of sodium bicarbonate from the particles, both prior to ingestion and in the stomach. The viscous aqueous medium is considered to delay release of the sodium bicarbonate from the ingested minitablets until the composition has reached the small intestine, where it is efficiently absorbed.

[0112] In one advantageous embodiment of the composition, the viscous aqueous medium is a viscoelastic medium, preferably. in the form of a gel. Minitablets are dispersed in the viscoelastic medium prior to ingestion of the combined products. Preferably, the viscoelastic medium is a gel, such as an aqueous semisolid gel with viscoelastic properties. The viscoelastic medium prevents sedimentation and facilitates ingestion of the particles. A further advantage of a viscoelastic vehicle is that it slows down mixing of the medium, e.g. when ingested, and thereby decreases the rate of erosion for the tablets in the composition. As demonstrated in Example 7, the viscoelastic vehicle is considered as useful to substantially delay release of the NaHCOs from the minitablets until the composition has been ingested.

[0113] One characteristic of a viscoelastic medium is that it has shear-thinning properties or pseudoplastic properties. Compared to a medium which is viscous but not viscoelastic, a viscoelastic medium is viscous when at rest, but less viscous when flowing at speed or when agitated, such as when being swallowed.

[0114] Referring to Example 9 and Fig. 7, viscosity can be e.g. determined at 20°C using a shear rate controlled rheometer (Model 302, Anton Paar, Germany), using a parallel plate geometry (plate diameter 50 mm, gap 100 pm). In this setup, the viscosity of water is approximately constant at 1 mPa s, at shear rates between 0 - 100 s’1. For avoidance of doubt, viscous aqueous media as defined herein are considerably more viscous than water. Viscous aqueous media as defined herein typically exhibit a viscosity of at least 50 mPa s, such as at least 100 mPa- s at shear rates between 0 - 100 s-1, such as at 40 s-1. Preferably, aqueous media as defined herein exhibit a viscosity of at least 300 mPa s, such as at least 500 mPa s at shear rates between 0 - 100 s’1, such as at 40 s’1. In addition to the viscous properties, viscoelastic media as defined herein typically exhibit a significantly higher viscosity at shear rates between 0 - 10 s’1than at shear rates between 20 - 100 s’1. Viscoelastic media as defined herein typically exhibit a typically exhibit a viscosity at a shear rate of 5 s’1that is at least twice the viscosity than at a shear rate of 40 s’1. The specific values above are relevant for this specific setup, but the skilled person can with reference to Example 9 easily determine corresponding values for viscosity and viscoelasticity in other experimental setups. For avoidance of doubt, the viscosity values determined refer to the viscous aqueous medium prior to combination with the ingestible particles, when this property can be determined with this experimental setup. The viscoelastic medium (vehicle) is advantageous as it slows down mixing of the medium, e.g. when ingested, and thereby decreases the rate of erosion for the tablets in the composition. In contact with water, bicarbonate will be released from the minitablets in a controlled manner. When minitablets are surrounded by the viscoelastic medium, the release will be slower than in a low-viscosity liquid, due to water close to the tablets being stagnant. In the stomach, the viscoelastic medium also will to some extent act as a barrier against the gastric juice.

[0115] In general, a gel can be described as a colloid in which the disperse phase has combined with the dispersion medium to produce a semisolid material with both viscous and elastic properties, where the elastic property dominates. Viscoelastic properties can be described by oscillatory tests, where phase shift between strain (y, dimensionless) and stress (T, N / m2) is measured. For phase shifts between 45° and 90°, fluid properties are dominating, while for phase shifts between 0° and 45°, elastic properties, typical for a gel, are dominating. The complex shear modulus can be described as a vector G having the perpendicular components G’ (storage of elastic energy, storage modulus) and G” (loss of energy by viscous dissipation, loss modulus). Thus, a gel is characterized by G’ being larger than G”. A system is gel-like at a given frequency as soon as G’ (storage modulus which concerns the solid-like response part of the material) is higher than G" (loss modulus which concerns the liquid-like response on the material).

[0116] Gelled products are characterized by having a relatively soft and chewy texture. Typical gelled products include gelatine based products as well as products based on certain types of carrageenan, alginate, starches, agarose, [3-glucan, gellan gum, pectin or cellulose compounds. In general, a gel can be described as a colloid in which a dispersed phase has combined with the dispersion medium to produce a semisolid material, e.g., a jelly.

[0117] In a gel, the gel structure will prevent tablets from sedimentation / sinking despite their high density. It also contributes to an improved perceived palatability for the composition. The gel will thereby also facilitate ingestion of the minitablets. For avoidance of doubt, the ingestible particles comprising sodium bicarbonate are not constituting the dispersed phase of the gel system. The ingestible particles comprising sodium bicarbonate are themselves dispersed in the gel. The gel, in turn, can be described as a colloid in which a dispersed phase (which is not the ingestible particles comprising sodium bicarbonate) has combined with the dispersion medium to produce a semisolid material.

[0118] In certain embodiments, the viscous aqueous medium comprises one or more natural polymers dissolved in water as a thickener. Preferred natural polymers are selected from polysaccharides, such as native and modified starch, xanthan gum, guar gum, karragenan, alginate, pectin, and combinations thereof. Modified starch provides viscoelastic properties to the medium with good stability. A preferred modified starch is acetylated distarch adipate, preferably in an amount of more than 2 wt%, such as more than 3 wt% of the viscous aqueous medium to obtain highly useful viscoleastic properties. For high palatability, a combination of starch and a smaller amount of a more potent thickener, such as xanthan gum is advantageous. Preferred natural polymers are a combination of

[0119] (a) native or modified starch; and

[0120] (b) xanthan gum or guar gum; in a relative weight ratio (a):(b) of from 99:1 to 90:10.

[0121] In a preferred embodiment, the viscous aqueous medium comprises starch or modified starch, preferably modified starch, as the natural polymers. These will be attacked by amylases, leading to weakening the gel, which will facilitate the release of sodium bicarbonate from the minitablets in the small intestine. Bicarbonate release is facilitated and expected to be completed before minitablets reach the colon.

[0122] In some embodiments, the viscous aqueous medium comprises one or more sugars or complex carbohydrates dissolved in water. Preferred sugars are selected from glucose, fructose, sucrose and isomaltulose. Preferred complex carbohydrates are selected from starch, maltodextrin, glucose syrup and fructose syrup.

[0123] The viscous aqueous medium could preferably have one of the following compositions (balanced with water to 100 wt%): (A) 4 - 12 wt% maltodextrin; 3 - 10 wt% fructose; 2 - 7 wt% acetylated distarch adipate; and 0.1 - 1.0 wt% xanthan gum.

[0124] (B) 6 - 14 wt% maltodextrin, 2 - 5 wt% fructose, 1 -3 wt% acetylated distarch adipate and 0.1 - 1.0 wt% xanthan gum.

[0125] In some embodiments of the composition, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is more than 10 g, preferably more than 15 g. In some embodiments of the composition, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g.

[0126] In one embodiment, the composition is a suspension comprising the ingestible particles dispersed in an aqueous medium. The particles have a size in the range of 1.2 - 5.0 mm, with a thickness in at least one dimension of 1 .2 - 2.0 mm. The particles contain more than 65 % (w / w) of the sodium bicarbonate salt. The ingestible particles are suspended in a viscous medium, e.g. containing maltodextrin and a sugar, such as fructose, dissolved in water, to facilitate intake and to improve palatability.

[0127] There is also provided a kit for preparing a sodium bicarbonate composition, the kit comprising ingestible particles as defined herein; and an aqueous medium as defined herein. The particles are added to the aqueous medium before ingestion. Alternatively, the kit is comprising ingestible particles as defined herein; dry components of the aqueous medium as defined herein; and optionally water. Preferably, water is not part of the kit but supplied separately when preparing the ingestible composition. The dry components are preferably presented as a powder. The particles may be mixed with the dry components, followed by addition of water to the mixture, thereby obtaining the particles in the aqueous medium. Preferably, the dry components are first mixed with water to obtain the aqueous medium, followed by addition of the particles. The aqueous medium should preferably be transparent with a thick consistency that can be spooned directly from the vessel used.

[0128] The kit is useful for preparing the composition as a suspension comprising the ingestible particles dispersed in the aqueous medium. The resulting composition is useful for preventing, alleviating or mitigating dystoci. In some embodiments, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is more than 10 g, preferably more than 15 g. In some embodiments of the composition, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g.

[0129] According to a further aspect, the ingestible particles are useful in a composition to prepare a pregnant woman for labor. Specifically, the ingestible particles are useful in the composition disclosed herein to prepare a pregnant woman for labor.

[0130] It is furthermore realized that the composition comprising the ingestible particles and the kit are useful to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia. The ingestible particles are as such useful to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia.

[0131] According to a further aspect, there is provided a method for of preparing a pregnant woman for labor, comprising the step of said pregnant woman ingesting the composition comprising the ingestible particles. Specifically, the composition is as defined herein. Preferably, the composition is freshly prepared by mixing the ingestible particles and the aqueous medium shortly before ingestion, e.g. less than 5 minutes before ingestion. This ensures that the particles are essentially intact and non-dissolved when ingested. Preferably, the dry components of the aqueous medium are first mixed with water to obtain the aqueous medium, followed by addition of the particles. The aqueous medium should preferably be transparent with a thick consistency that can be spooned directly from the vessel used.

[0132] There is provided a method to prevent, alleviate or mitigate labor- induced acidosis and / or acidemia in a pregnant female subject, comprising the step of ingesting the composition comprising the ingestible particles. Typically, ingestible particles containing a total amount of 0.10 - 0.40 g sodium bicarbonate salt I kg body mass are thereby ingested; preferably 0.20 -0.35 g sodium bicarbonate salt I kg body mass; preferably 0.25 -0.30 g sodium bicarbonate salt / kg body mass. In a preferred use or method as defined herein, ingestible particles containing a total amount of 0.10 - 0.40 g sodium bicarbonate salt I kg body mass are thereby ingested; preferably 0.20 -0.35 g sodium bicarbonate salt I kg body mass; preferably 0.25 -0.30 g sodium bicarbonate salt I kg body mass. It is preferred that a sufficient amount of sodium bicarbonate is ingested so as to achieve an increase of the blood bicarbonate concentration of at least 4 mmol / l, such as at least 6 mmol / l. It is however realized that already an increase of the blood bicarbonate concentration of 1 mmol / , 2 mmol / l, or 3 mmol / l can be useful, depending on the situation.

[0133] The present invention will in the following be further illustrated by the following non-limiting examples.

[0134] Examples

[0135] Example 1

[0136] Minitablets with a diameter of 3.0 mm, a height of 1 .5 mm and a mean weight of 18 mg were produced with the following composition: NaHCOs 85 wt %, Calcium phosphate 10 wt %, gum acacia 2.5 wt %, magnesium stearate 2 wt % and anhydrous colloidal silica 0.5 wt %. Components were mixed in a Turbula mixer. The tablets were compressed using a Fette 52i rotary press, equipped with a force feeder.

[0137] Participants had taken a breakfast at least 3 h prior to ingestion of sodium bicarbonate minitablets and vehicle. A viscous vehicle was prepared by blending 22 g maltodextrin, 16 g fructose, 12 g acetylated di-starch adipate and 0.4 g xanthan gum and mixing the blend with 300 g of water. The mixture was ready to use 10 min after mixing. Sodium bicarbonate minitablets corresponding to 0.3 g sodium bicarbonate per kilo bodyweight were added to the mixture and all was ingested within 5 min.

[0138] Arterialized capillary blood samples were collected before ingestion and at 30, 60 or 120 min intervals until 8 h after intake. Blood samples were analyzed immediately on a blood gas analyzer.

[0139] Fig. 1 shows plasma standard bicarbonate concentrations (mean + / - S.D., n=4) measured before and after ingestion of minitablets, corresponding to 0.30 g NaHCOs per kilo bodyweight, taken together with 350 g of viscous drink.

[0140] At least 90 % of the peak bicarbonate concentration was reached at 120 min. The maximum increase from t=0 was around 7 mmol / l.

[0141] Example 2.

[0142] Minitablets as in Example 1 were used.

[0143] The participant had taken a breakfast at least 3 h prior to ingestion of sodium bicarbonate minitablets and vehicle. A viscous vehicle was prepared by blending 33 g maltodextrin, 11 g fructose, 5.4 g acetylated di-starch adipate and 0.6 g xanthan gum and mixing the blend with 300 g of water (intermediate viscosity). Sodium bicarbonate minitablets corresponding to 0.3 g sodium bicarbonate per kilo bodyweight were added to the mixture and all was ingested within 5 min. A light meal was taken at 60 min, consisting of two rice cakes with almond butter and of a drink containing 26 g of maltodextrin and 13 g of fructose dissolved in 300 g water.

[0144] On one of the two experiment days (dashed line in Figure 2), three 20- min high intensity interval training (HI IT) exercises were conducted, starting at about 3, 5 and 7 h respectively after sodium bicarbonate intake. Arterialized capillary blood samples were collected before and until about 8.5 h after intake.

[0145] Fig. 2 shows (A) plasma standard bicarbonate concentrations and (B) extracellular fluid base excess, BE (Ecf), measured before and after ingestion of minitablets corresponding to 0.30 g NaHCOs per kilo bodyweight, taken together with 350 g of the viscous drink (intermediate viscosity). Solid line: Resting or low intensity exercise (walking) conditions.

[0146] Dashed line: Resting and low intensity exercise interrupted by three 20-min high intensity interval training (H I IT) sessions, starting after blood sampling at about 180, 300 and 420 min respectively.

[0147] Plasma bicarbonate and BE (Ecf) were lowered by HI IT sessions but were restored before next HUT session and at the end of the trial, compared to plasma bicarbonate levels during resting / low intensity exercise conditions (Fig. 2 A, B)). Example 3

[0148] Minitablets as in Example 1 and 2 were used in combination with either a high viscosity vehicle as in Example 1 , or a vehicle with intermediate viscosity, as in Example 2. Mixtures containing minitablets corresponding to 0.30 g sodium bicarbonate per kg bodyweight were ingested 2.5-3.5 h after a standard breakfast meal. Standard bicarbonate levels in arterialized capillary blood were monitored shortly before and after intake.

[0149] Fig. 3 shows uptake of bicarbonate from minitablets in combination with either a high-viscosity vehicle (solid lines B and C) or a vehicle of intermediate viscosity (dashed line A). In samples A and B, a light meal was taken at 60 min. In sample C, no light meal was taken.

[0150] As seen in Fig. 3, standard bicarbonate levels in arterialized capillary blood, monitored shortly before and after intake indicated a faster uptake of bicarbonate during the first 120 min after intake using the high-viscosity vehicle (B and C), possibly due to faster gastric emptying. A light meal taken at 60 min (consisting of two rice cakes with almond butter and of a drink containing 26 g of maltodextrin and 13 g of fructose dissolved in 300 g water) affected uptake of bicarbonate during the following 90-120 min (A and B).

[0151] Example 4

[0152] Different sodium bicarbonate formulations, each in combination with a vehicle, were ingested by 2-6 subjects on 1-4 occasions. Perceived palatability as well as perceived upper and lower gastrointestinal symptoms 0-6 h after ingestion were recorded. Standard bicarbonate concentrations in capillary blood were monitored before ingestion and up to at least 210 min after ingestion. Results are summarized in Table 1. Examples of bicarbonate levels from single experiments are given in Fig. 4.

[0153] Fig. 4 shows blood plasma bicarbonate levels in two different subjects measured after intake of

[0154] A: Sodium bicarbonate dissolved in 480 mL of water, containing 33 g of maltodextrin and 17 g of sucrose;

[0155] B: Sodium bicarbonate powder (<0.3 mm) mixed with vehicle as in Example 1 directly prior to ingestion;

[0156] D1 and D2: Two identical experiments with sodium bicarbonate minitablets and viscous vehicle as in Example 1.

[0157] Table 1

[0158] Perceived palatability and Gl symptoms and time to reach 90 % of maximum blood plasma bicarbonate concentration (T90% max) after ingestion of different bicarbonate and vehicle formulations.

[0159] A: Sodium bicarbonate dissolved in low viscosity vehicle (sucrose 33 g, maltodextrin 17 g, 480 ml water).

[0160] B: Sodium bicarbonate powder added to high viscosity vehicle just before ingestion.

[0161] C: Sodium bicarbonate granulate.

[0162] D and E: minitablets as in Example 1-3, containing 85% sodium bicarbonate. F: Placebo minitablets where sodium bicarbonate was replaced by calcium carbonate (50%) and maltodextrin (35%).

[0163] G: Minitablets as in Example 1-3, wherein calcium phosphate and gum acacia is replaced by 10 wt % PVP. Sodium bicarbonate content is 87.5 wt %.

[0164] H: Minitablets as in G, with an enteric coating of Eudragit® L30D55.

[0165] I: Hypromellose capsules, size 00E, filled with 1.2 g sodium bicarbonate powder (<0.3 mm)

[0166] High viscosity vehicle as described in Example 1 .

[0167] Intermediate viscosity vehicle as described in Example 2.

[0168] Palatability: 1 = very low, 5 = very high.

[0169] Upper and lower Gl symptoms: 1 = no symptoms, 4-5= severe symptoms.

[0170] Example 5

[0171] Minitablets as in Example 1 containing 85% NaHCOs were compared with sodium bicarbonate granulate of particle size 0.5-1 .0 mm (sample C in Table 1 ) in terms of in vitro dissolution rate.

[0172] Minitablets or granulate corresponding to 138 mg of sodium bicarbonate were added to 30 ml of simulated intestinal fluid, placed in 50-ml screw capped containers. The containers were intermittently gently shaken during the experiment and pH was measured over time, see Fig. 5.

[0173] The rise in pH caused by bicarbonate is substantially delayed with the minitablets compared to the small granules. Example 6

[0174] (A) Minitablets with a diameter within the range of 1.2 - 5.0 mm and a thickness within the range of 1.2 - 2.0 mm were produced with the following composition:

[0175] Sodium bicarbonate 80 wt % Calcium carbonate 8 wt % Hydroxypropyl cellulose 7 wt % Maltodextrin 0.5 wt % Gum acacia 2 wt % Magnesium stearate 2 wt % Anhydrous colloidal silica 0.5 %.

[0176] (B) Minitablets with a diameter within the range of 1.2 - 5.0 mm and a thickness within the range of 1.2 - 2.0 mm are produced with the following composition:

[0177] Sodium bicarbonate 87.5 wt % Hydroxypropyl cellulose 10 wt % Magnesium stearate 2 wt % Anhydrous colloidal silica 0.5 %.

[0178] Example 7

[0179] Release of sodium bicarbonate from minitablets in three different experiments.

[0180] (A) An equipment similar to the dissolution apparatus of type 2, according to the European Pharmacopoeia (Ph. Eur.) 2.9.3 “Dissolution test for solid dosage forms” was used. Eight minitablets, size 1 .5 x 3.0 mm, with a total weight of 144 mg, containing 126 mg NaHCOs and excipients as in Example 6B, were placed on a stainless steel net 40 mm above the bottom of a 500-ml glass beaker, and 25 mm above a magnetic stirring bar rotating. Demineralized water (500 ml) was kept at 37 + / - 2 °C and stirred at 150 rpm. The concentration of dissolved NaHCOs, was determined by electric conductivity measurement. As a reference for complete release, conductivity was measured when remains of the tablets could no longer be observed and the conductivity did not increase further within three minutes. More than 75% of the NaHCOs was released within 15 min and more than 95% within 30 min from minitablets in demineralized water.

[0181] (B) Six containers, each containing eight minitablets as in (A) above were dispersed in 40 g of a viscoelastic medium, a semisolid gel as described in Example 1 , and were tumbled at 12 rpm in an incubator kept at 37 °C. Containers were taken out at different time points and after removing and gently washing the minitablets with demineralized water, the gel and wash liquid were mixed and diluted to a total weight of 200 g. The NaHCOs concentration was measured by electric conductivity measurement. As a reference for complete release, eight minitablets were kept in 160 ml of demineralized water until totally disintegrated and then mixed with 40 g of gel. When minitablets were kept dispersed in slowly tumbled gel, about 25% of the NaHCOs was released within 15 min, about 50% within 30 min and about 75% within 60 min.

[0182] (C) Minitablets were dispersed and kept in gel for 15 min at room temperature. The amount NaCOs released was determined as in (B). When minitablets were kept dispersed in a gel at room temperature without tumbling, about 10-15% of NaCOs was released within 15 min.

[0183] The results are presented in Fig. 6, wherein the released percentage of NaHCOs from the minitablets is shown over time for experiments (A)-(C) as detailed above.

[0184] It is concluded from these experiments that the release of NaHCOs from the minitablets is considerably slower when they are tumbled in a viscoelastic gel vehicle (B) compared to when stirred in a water vehicle (A). In the context of the present invention, the viscoelastic vehicle is considered as useful to delay release of the NaHCOs from the ingested minitablets until the composition has reached the small intestine. It is also concluded that when the mini-tablets are dispersed in a gel that is not tumbled (C), the release of NaHCOs from the minitablets is considerably slower than when tumbled (B). In the context of the present invention, the viscoelastic vehicle is considered as useful to substantially delay release of the NaHCOs from the minitablets until the composition has been ingested. About 10-15% of NaCOs was released within 15 min in experiment (C), within which time it is suggested to ingest the product.

[0185] Example 8

[0186] Viscoelastic vehicles were tested for sedimentation rate of bicarbonate minitablets as defined herein.

[0187] The tablets were of diameter 3 mm, height 1 .5 mm, weight 18 mg and density 2.0 mg / mm3A few tablets were placed beneath the surface of the vehicle and observed for up to 30 min or until having sedimented at least 10 mm.

[0188] Vehicle A (A 100%) contained 27 g maltodextrin, 20 g fructose, 15 g acetylated di-starch adipate, 0.5 g xanthan gum, 300 ml water. Dilutions of A with water were also prepared, termed A 80% - A 67%. The vehicle A 67% corresponds to a dilution of A 100% by a factor 1 .5. Vehicle E1 is a composition as in Example 1. Vehicle E2 is a composition as in Example 2.

[0189] The sedimentation rates for the tested vehicles are presented in Table 2.

[0190] Table 2

[0191] Example 9

[0192] (A) Viscosity and shear-thinning properties of the two vehicles A 100% and A 67% from Example 8 were measured using a share rate controlled rheometer (Model 302, Anton Paar, Germany). A parallel plate geometry was used (plate diameter 50 mm, gap 100 pm). Viscosity was measured at 20°C. The viscosities for the vehicles are presented in Fig. 7 (A-100: black filled circles, upper curve; and A-67: non-filled circles, mid curve). The relative viscosity A-100 / A-67: grey filled circles, lower curve is also presented in Fig. 7.

[0193] As seen in Fig. 7, the viscosity curves of the two hydrocolloid dispersions A-100 and A-67 exhibit shear thinning properties. Viscosities at shear rate 5 s-1: A-100: 5900 mPa s; A-67 560 mPa s. Viscosities at shear rate 40 s-1: A-100: 1540 mPa s; A-67 220 mPa s.

[0194] Viscosity of A-67, obtained by diluting vehicle A-100 by a factor 1 .5, resulted in a decrease in viscosity by a factor of about 6 or more, depending on shear rate, as shown in Fig. 7.

[0195] (B) An oscillatory test showing elastic component G’ (storage modulus) and viscous component G” (loss modulus) of complex shear vector G was conducted for Vehicle A (A 100%) from Example 8.

[0196] Measurements were made at 20°C using a shear rate controlled rheometer (Model 302, Anton Paar, Germany). A parallel plate geometry was used (plate diameter 50 mm, gap 100 pm).

[0197] The storage modulus G’ (squares) and the loss modulus G” (triangles) for A 100% are shown in Fig. 8. The ratio G7G” is about 3 which means that the sample is a viscoelastic medium and has the properties of a gel.

[0198] Example 10

[0199] A well-trained male athlete, body weight 80 kg, performed high- intensity interval training on two consecutive days, following the same exercise protocol on each day. Blood pH and plasma bicarbonate were measured before, during and after high-intensity interval training. After warmup, 45-s running and 15-s resting was repeated 30 times starting at time 0 with a five min break half-way. Exercise intensity exceeded the anaerobic threshold (plasma lactate exceeding 4 mmol / l). On the second day, a composition as defined herein was ingested prior to exercise, shortly after the sampling at time -90 min. The composition contained minitablets as described in Example 7 containing 22 g NaHCOs, corresponding to 0.275 g / kg body weight, dispersed in a semisolid vehicle as described in Example 1.

[0200] The results are presented in Fig. 9, wherein the upper panel (A) shows blood pH and the lower panel (B) shows plasma bicarbonate concentration. Grey bars illustrate the high-intensity interval training intervals.

[0201] Day 1 : circles / dotted line; Day 2: squares / solid line.

[0202] On the first day (control), exercise resulted in a drop in pH from pH 7.43 to pH 7.35, and a drop in plasma bicarbonate concentration from 24 mmol / l to 18 mmol / l, corresponding to a mild acidosis. On the second day, a pH drop caused by exercise was counteracted by a pH increase caused by ongoing uptake bicarbonate from the ingested composition. The blood pH remained above 7.40 and the plasma bicarbonate concentration remained above 23 mmol / l. The changes in blood pH and plasma bicarbonate followed the same pattern, as can be seen in Fig. 9

[0203] Example 11

[0204] A well-trained female athlete, body weight 52 kg, performed high- intensity interval training on a treadmill on two separate days, following the same exercise protocol on each day. Plasma bicarbonate and extracellular fluid base excess, BE (Ecf), were measured before, during and after high- intensity interval training. After 20 min warm-up, 45-s running and 15-s resting was repeated in three blocks of ten repetitions with two minutes break between the blocks. Exercise intensity exceeded the anaerobic threshold (plasma lactate exceeding 4 mmol / l). On the first day, a composition as defined herein was ingested 100 min prior to exercise (time zero, t=0 min), shortly after the first sampling at time at -5 min. The composition contained minitablets as described in Example 7 containing 13 g NaHCOs, corresponding to 0.25 g / kg body weight, dispersed in a semisolid vehicle as described in Example 1 . Four days later, the procedure was repeated, now with intake of semisolid vehicle without bicarbonate minitablets.

[0205] The results are presented in Fig. 10, wherein the upper panel (A) shows changes in plasma standard bicarbonate and the lower panel (B) shows changes in extracellular fluid base excess, BE (Ecf). Day 1 : circles / solid line; Day 2: squares / dotted line.

[0206] On the first day, plasma bicarbonate and BE (Ecf) increased by 5.6 mmol / l and 7.6 mmol / l respectively after bicarbonate intake and before start of exercise. Exercise resulted in a drop in both plasma bicarbonate and BE (Ecf) back to the initial level. Already 15 min later, bicarbonate and BE (Ecf) levels were higher by about 5 mmol / l and 7 mmol / l compared to initial levels. In contrast to this, exercise on Day 2, without bicarbonate intake, resulted in a plasma bicarbonate concentration of 19.6 mmol / l, 2.7 mmol / l lower than the initial level and indicative of mild acidosis. Similarly, BE (Ecf) showed a marked temporary decrease as result of the exercise. In summary, intake of bicarbonate prevented plasma bicarbonate and BE (Ecf) levels to drop below normal values as result of the exercise.

[0207] Example 12

[0208] A randomized controlled trial of women in active labor is performed. Women are administered a composition comprising the ingestible particles, wherein the particles contain more than 10 g of sodium bicarbonate.

[0209] The composition contains minitablets as described in Example 7 containing 22 g NaHCOs, corresponding to 0.275 g / kg body weight, dispersed in a semisolid vehicle as described in Example 1 .

[0210] Perceived palatability as well as perceived upper and lower gastrointestinal symptoms 0-6 h after ingestion are recorded.

[0211] A first group of women are administered the composition early, when the onset of labor has been determined to have occurred. A second group of women are administered the composition after they have been diagnosed with dystocia. A third group of women are administered the composition approximately 1 h before stimulation with oxytocin is started.

[0212] Blood pH and plasma bicarbonate are measured before, during and after ingestion until delivery. ITEMIZED LIST OF EMBODIMENTS

[0213] 1 . A composition which is a suspension comprising ingestible particles comprising sodium bicarbonate, dispersed in an aqueous medium; wherein the particles are tablets with a thickness of 1 .0 - 2.0 mm and a diameter of

[0214] 1 .0 - 5.0 mm; and wherein the particles contain more than 50 % (w / w) of the sodium bicarbonate; and wherein the aqueous medium is a viscous aqueous medium, for use in preventing, alleviating or mitigating dystocic labor.

[0215] 2. A composition for use according to item 1 , wherein the ingestible particles comprise more than 65 % (w / w) of the sodium bicarbonate, such as more than 75 % (w / w) of the sodium bicarbonate.

[0216] 3. A composition for use according to any one of the preceding items, wherein the ingestible particles comprise less than 90 % (w / w) of the sodium bicarbonate, such as less than or equal to 85 % (w / w) of the sodium bicarbonate.

[0217] 4. A composition for use according to any one of the preceding items, wherein the ingestible particles are suitable for releasing the sodium bicarbonate in the lower intestine.

[0218] 5. A composition for use according to any one of the preceding items, wherein the tablets have a thickness of 1 .2 - 2.0 mm and a diameter of 1 .2 - 5.0 mm.

[0219] 6. A composition for use according to any one of the preceding items, wherein the tablets have a thickness of < 1 .8 mm, such as < 1 .5 mm.

[0220] 7. A composition for use according to any one of the preceding items, wherein the tablets have a diameter of < 4.0 mm, such as < 3.0 mm.

[0221] 8. A composition for use according to item 7, wherein the tablets have a diameter of < 2.0 mm, such as < 1.8 mm. 9. A composition for use according to any one of the preceding items, wherein the ingestible particles are non-disintegrating.

[0222] 10. A composition for use according to any one of the preceding items, wherein the ingestible particles are without any coating, such as without any enteric coating.

[0223] 11 . A composition for use according to any one of the preceding items, wherein the ingestible particles are non-layered particles.

[0224] 12. A composition for use according to any one of the preceding items, wherein the ingestible particles are further comprising a binder.

[0225] 13. A composition for use according to item 12, wherein the binder is selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropyl cellulose (HPC), microcrystalline cellulose, gelatin and polysaccharides, and combinations thereof.

[0226] 14. A composition for use according to item 13, wherein the binder is selected from hydroxypropyl cellulose (HPC) and combinations thereof.

[0227] 15. A composition for use according to item 13, wherein the polysaccharides are selected from high molecular weight alginates, pectins, gum tragacanth and gum acacia, and combinations thereof.

[0228] 16. A composition for use according to item 12, wherein the binder is selected from calcium carbonate and gum acacia, and combinations thereof.

[0229] 17. A composition for use according to any one of the preceding items, wherein the ingestible particles are further comprising a lubricant. 18. A composition for use according to item 17, wherein the lubricant is selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof; preferably wherein the lubricant is magnesium stearate.

[0230] 19. A composition for use according to any one of the preceding items, wherein the ingestible particles are further comprising a glidant.

[0231] 20. A composition for use according to item 19, wherein the glidant is fumed silica.

[0232] 21 . A composition for use according to any one of the preceding items, wherein the ingestible particles are comprising further excipients selected from sugars and complex carbohydrates.

[0233] 22. A composition for use according to item 21 , wherein the sugars are selected from glucose, fructose, sucrose and isomaltulose.

[0234] 23. A composition for use according to item 21 , wherein the the complex carbohydrates are selected from starch, maltodextrin, dried glucose syrup and dried fructose syrup.

[0235] 24. A composition for use according to any one of items 1 and 4-11 , wherein the ingestible particles have the following composition:

[0236] Sodium bicarbonate 75 - 85 wt %; Calcium carbonate 5 - 10 wt %;

[0237] Hydroxypropyl cellulose 5 - 10 wt %; Maltodextrin 0.1 - 1.0 wt %; Gum acacia 1 - 3 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0238] 25. A composition for use according to any one of items 1 and 4-11 , wherein the ingestible particles have the following composition:

[0239] Sodium bicarbonate 82 - 92 wt %; Hydroxypropyl cellulose 5 - 15 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1.0 %. 26. A composition for use according to any one of items 1 and 4-11 , wherein the ingestible particles have the following composition:

[0240] Sodium bicarbonate 80 - 90 wt %; Calcium phosphate 5- 15 wt %; Gum acacia 1 - 5 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0241] 27. A composition for use according to any of the preceding items, wherein the sedimentation rate of a single ingestible particle in the unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min.

[0242] 28. A composition for use according to any one of the preceding items, wherein the viscous aqueous medium is a viscoelastic medium.

[0243] 29. A composition for use according to any one of the preceding items, wherein the viscous aqueous medium is a liquid.

[0244] 30. A composition for use according to item 28, wherein the viscoelastic medium is a gel.

[0245] 31 . A composition for use according to any one of the preceding items, wherein the viscous aqueous medium comprises one or more natural polymers dissolved in water as a thickener.

[0246] 32. A composition for use according to item 31 , wherein the natural polymers are selected from polysaccharides, such as native and modified starch, xanthan gum, guar gum, karragenan, alginate, pectin, and combinations thereof.

[0247] 33. A composition for use according to item 32, wherein the natural polymers are a combination of

[0248] (a) native or modified starch; and (b) xanthan gum or guar gum; in a relative weight ratio (a):(b) of from 99:1 to 90:10.

[0249] 34. A composition for use according to item 32, wherein the natural polymers are selected from native and modified starch.

[0250] 35. A composition for use according to item 34, wherein the natural polymers are modified starch.

[0251] 36. A composition for use according to any one of the preceding items, wherein the viscous aqueous medium comprises one or more sugars or complex carbohydrates dissolved in water.

[0252] 37. A composition for use according to item 36 wherein the sugars are selected from glucose, fructose, sucrose and isomaltulose.

[0253] 38. A composition for use according to item 36, wherein the complex carbohydrates are selected from starch, maltodextrin, glucose syrup and fructose syrup.

[0254] 39. A composition for use according to any one of items 1-30, wherein the viscous aqueous medium has the following composition:

[0255] 4 - 12 wt% maltodextrin; 3 - 10 wt% fructose; 2 - 7 wt% acetylated distarch adipate; and 0.1 - 1.0 wt% xanthan gum; in water to 100 wt%.

[0256] 40. A composition for use according to any one of items 1-30, wherein the viscous aqueous medium has the following composition:

[0257] 6 - 14 wt% maltodextrin, 2 - 5 wt% fructose, 1 -3 wt% acetylated distarch adipate and 0.1 - 1.0 wt% xanthan gum; in water to 100 wt%.

[0258] 41 . A composition for use according to any one of the preceding items, wherein the total amount of sodium bicarbonate in the ingestible particles in one serving is more than 10 g, preferably more than 15 g. 42. A composition for use according to item 41 , wherein the total amount of sodium bicarbonate in the ingestible particles in one serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g.

[0259] 43. A composition for use according to any one of the preceding items, wherein the ingestible particles are supplied at the same time as, prior to, or after administering oxytocin or oxytocin analogs.

[0260] 44. A composition for use according to item 43, wherein the ingestible particles are supplied 30 min - 5 hours prior to supplying oxytocin or oxytocin analogs.

[0261] 45. A kit for preparing a sodium bicarbonate composition, the kit comprising ingestible particles and an aqueous medium as defined in any one of the preceding items, wherein the kit is for use in preventing, alleviating or mitigating dystocic labor.

[0262] 46. A kit for preparing a sodium bicarbonate composition, the kit comprising ingestible particles as in any one of the preceding items; dry components of the aqueous medium as defined in any one of the preceding items; and optionally water, wherein the kit is for use in preventing, alleviating or mitigating dystocic labor.

[0263] 47. Use of a composition according to any one of items 1 -42 or a kit according to any one of items 45-46 to prepare a pregnant woman for labor.

[0264] 48. Use of a composition according to any one of items 1 -42 or a kit according to any one of items 45-46 to prevent, alleviate or mitigate labor- induced acidosis and / or acidemia in a pregnant woman. 49. A method of preparing a pregnant woman for labor, comprising the step of said pregnant woman ingesting a composition comprising ingestible particles according to any one of items 1-42.

[0265] 50. A method for preventing, alleviating or mitigating labor-induced acidosis and / or acidemia in a pregnant female subject, comprising the step of ingesting a composition according to any one of items 1-42.

[0266] 51 . A method of treating labor-induced acidosis and / or acidemia in a human subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of a composition according to any one of items 1-42.

[0267] 52. A method of preventing, alleviating or mitigating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of a composition according to any one of items 1-42.

[0268] 53. A method of treating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of a composition according to any one of items 1-42.

[0269] 54. A method according to any one of items 50-53, wherein the ingestible particles are supplied at the same time as, prior to, or after administering oxytocin or oxytocin analogs.

[0270] 55. A method according to item 54, wherein the ingestible particles are supplied 30 min - 5 hours prior to supplying oxytocin or oxytocin analogs.

[0271] 56. A method according to any one of items 49-55, wherein ingestible particles containing a total amount of 0.10 - 0.40 g sodium bicarbonate salt I kg body mass are thereby ingested; preferably 0.20 -0.35 g sodium bicarbonate salt I kg body mass; preferably 0.25 -0.30 g sodium bicarbonate salt / kg body mass. 57. Use of a composition according to any one of items 1 -42 or a kit according to any one of items 45-46 in the preparation of a medicament for preventing, alleviating or mitigating dystocic labor.

[0272] 58. An ingestible particle comprising sodium bicarbonate, wherein the particle is a tablet with a thickness of 1 .0 - 2.0 mm and a diameter of 1 .0 - 5.0 mm; and wherein the particle contains more than 50 % (w / w) of the sodium bicarbonate, for use in preventing, alleviating or mitigating dystocic labor.

[0273] 59. An ingestible particle for use according to item 58, comprising more than 65 % (w / w) of the sodium bicarbonate, such as more than 75 % (w / w) of the sodium bicarbonate.

[0274] 60. An ingestible particle for use according to any one of items 58-59, comprising less than 90 % (w / w) of the sodium bicarbonate, such as less than or equal to 85 % (w / w) of the sodium bicarbonate.

[0275] 61 . An ingestible particle for use according to any one of items 58-60, wherein the particle is suitable for releasing the sodium bicarbonate in the lower intestine.

[0276] 62. An ingestible particle for use according to any one of items 58-61 , wherein the tablet has a thickness of 1 .2 - 2.0 mm and a diameter of 1 .2 - 5.0 mm.

[0277] 63. An ingestible particle for use according to any one of items 58-62, wherein the tablet has a thickness of < 1 .8 mm, such as < 1 .5 mm.

[0278] 64. An ingestible particle for use according to any one of items 58-63, wherein the tablet has a diameter of < 4.0 mm, such as < 3.0 mm.

[0279] 65. An ingestible particle for use according to item 64, wherein the tablet has a diameter of < 2.0 mm, such as < 1 .8 mm. 66. An ingestible particle for use according to any one of items 58-65, wherein the particle is non-disintegrating.

[0280] 67. An ingestible particle for use according to any one of items 58-66, without any coating, such as without any enteric coating.

[0281] 68. An ingestible particle for use according to any one of items 58-67, wherein the ingestible particle is a non-layered particle.

[0282] 69. An ingestible particle for use according to any one of items 58-68, further comprising a binder.

[0283] 70. An ingestible particle for use according to item 69, wherein the binder is selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropyl cellulose (HPC), microcrystalline cellulose, gelatin and polysaccharides, and combinations thereof.

[0284] 71 . An ingestible particle for use according to item 70, wherein the binder is selected from hydroxypropyl cellulose (HPC) and combinations thereof.

[0285] 72. An ingestible particle for use according to item 70, wherein the polysaccharides are selected from high molecular weight alginates, pectins, gum tragacanth and gum acacia, and combinations thereof.

[0286] 73. An ingestible particle for use according to item 69, wherein the binder is selected from calcium carbonate and gum acacia, and combinations thereof.

[0287] 74. An ingestible particle for use according to any one of items 58-73, further comprising a lubricant. 75. An ingestible particle for use according to item 74, wherein the lubricant is selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof.

[0288] 76. An ingestible particle for use according to item 75, wherein the lubricant is magnesium stearate.

[0289] 77. An ingestible particle for use according to any one of items 58-76, further comprising a glidant.

[0290] 78. An ingestible particle for use according to item 77, wherein the glidant is fumed silica.

[0291] 79. An ingestible particle for use according to any one of items 58-78, comprising further excipients selected from sugars and complex carbohydrates.

[0292] 80. An ingestible particle for use according to item 79, wherein the sugars are selected from glucose, fructose, sucrose and isomaltulose.

[0293] 81 . An ingestible particle for use according to item 79, wherein the the complex carbohydrates are selected from starch, maltodextrin, dried glucose syrup and dried fructose syrup.

[0294] 82. An ingestible particle for use according to any one of items 58 and 61-69, wherein the ingestible particle has the following composition:

[0295] Sodium bicarbonate 75 - 85 wt %; Calcium carbonate 5 - 10 wt %;

[0296] Hydroxypropyl cellulose 5 - 10 wt %; Maltodextrin 0.1 - 1.0 wt %; Gum acacia 1 - 3 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0297] 83. An ingestible particle for use according to any one of items 58 and 61-69, wherein the ingestible particle has the following composition: Sodium bicarbonate 82 - 92 wt %; Hydroxypropyl cellulose 5 - 15 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1.0 %.

[0298] 84. An ingestible particle for use according to any one of items 58 and 61-69, wherein the ingestible particle has the following composition:

[0299] Sodium bicarbonate 80 - 90 wt %; Calcium phosphate 5- 15 wt %; Gum acacia 1 - 5 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1 .0 wt %.

[0300] 85. An ingestible particle for use according to any one of items 58-84, wherein the ingestible particle is supplied at the same time as, prior to, or after administering oxytocin or oxytocin analogs.

[0301] 86. An ingestible particle for use according to item 85, wherein the ingestible particles are supplied 30 min - 5 hours prior to supplying oxytocin or oxytocin analogs.

[0302] 87. Use of ingestible particles according to any one of items 58-84 in a composition to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia in a pregnant woman.

[0303] 88. Use of ingestible particles according to any one of items 58-84 to prevent, alleviate or mitigate labor-induced acidosis and / or acidemia.

[0304] 89. A method of preparing a pregnant woman for labor, comprising the step of said pregnant woman ingesting the ingestible particles according to any one of items 58-84.

[0305] 90. A method for preventing, alleviating or mitigating labor-induced acidosis and / or acidemia in a pregnant female subject, comprising the step of ingesting the ingestible particles according to any one of items 58-84. 91 . A method of treating labor-induced acidosis and / or acidemia in a human subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the ingestible particles according to any one of items 58- 84.

[0306] 92. A method of preventing, alleviating or mitigating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the ingestible particles according to any one of items 58-84.

[0307] 93. A method of treating dystocic labor in a pregnant female subject in need thereof, comprising the step of ingesting a pharmaceutically effective amount of the ingestible particles according to any one of items 58-84.

[0308] 94. A method according to any one of items 90-93, wherein the ingestible particles are supplied at the same time as, prior to, or after administering oxytocin or oxytocin analogs.

[0309] 95. A method according to item 94, wherein the ingestible particles are supplied 30 min - 5 hours prior to supplying oxytocin or oxytocin analogs.

[0310] 96. A method according to any one of items 89-95, wherein ingestible particles containing a total amount of 0.10 - 0.40 g sodium bicarbonate salt I kg body mass are thereby ingested; preferably 0.20 -0.35 g sodium bicarbonate salt I kg body mass; preferably 0.25 -0.30 g sodium bicarbonate salt / kg body mass.

[0311] 97. Use of ingestible particles according to any one of items 56-82 in the preparation of a medicament for preventing, alleviating or mitigating dystocic labor.

Claims

CLAIMS1 . A composition which is a suspension comprising ingestible particles comprising sodium bicarbonate, dispersed in an aqueous medium; wherein the particles are tablets with a thickness of 1 .0 - 2.0 mm and a diameter of1 .0 - 5.0 mm; and wherein the particles contain more than 50 % (w / w) of the sodium bicarbonate; and wherein the aqueous medium is a viscous aqueous medium, for use in preventing, alleviating or mitigating dystocic labor.

2. A composition for use according to any one of the preceding claims, wherein the tablets have a thickness of 1.2 - 2.0 mm and a diameter of 1 .2 - 5.0 mm.

3. A composition for use according to claim 2, wherein the tablets have a diameter of < 2.0 mm, such as < 1.8 mm.

4. A composition for use according to any one of the preceding claims, wherein the ingestible particles are without any coating, such as without any enteric coating.

5. A composition for use according to any one the preceding claims, wherein the ingestible particles have the following composition:Sodium bicarbonate 82 - 92 wt %; Hydroxypropyl cellulose 5 - 15 wt %; Magnesium stearate 1 - 3 wt %; and Anhydrous colloidal silica 0.1 - 1.0 %.

6. A composition for use according to any of the preceding claims, wherein the sedimentation rate of a single ingestible particle in the unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min.

7. A composition for use according to any one of the preceding claims, wherein the viscous aqueous medium is a viscoelastic medium.

8. A composition for use according to claim 7, wherein the viscoelastic medium is a gel.

9. A composition for use according to any one of claims 7-8, wherein the suspension is ingested within 15 minutes after preparation.

10. A composition for use according to any one of the preceding claims, wherein the viscous aqueous medium has the following composition: 4 - 12 wt% maltodextrin; 3 - 10 wt% fructose; 2 - 7 wt% acetylated distarch adipate; and 0.1 - 1.0 wt% xanthan gum; in water to 100 wt%.11 . A composition for use according to any one of the preceding claims, wherein the viscous aqueous medium has the following composition:6 - 14 wt% maltodextrin, 2 - 5 wt% fructose, 1 -3 wt% acetylated distarch adipate and 0.1 - 1.0 wt% xanthan gum; in water to 100 wt%.

12. A composition for use according to any one of the preceding claims, wherein the ingestible particles are supplied at the same time as, prior to, or after administering oxytocin.

13. A kit for preparing a sodium bicarbonate composition, the kit comprising (i) ingestible particles comprising sodium bicarbonate; wherein the particles are tablets with a thickness of 1 .0 - 2.0 mm and a diameter of 1.0 - 5.0 mm; and wherein the particles contain more than 50 % (w / w) of the sodium bicarbonate; and (ii) an aqueous medium which is a viscous aqueous medium, wherein the kit is for use in preventing, alleviating or mitigating dystocic labor.

14. A kit for preparing a sodium bicarbonate composition, the kit comprising (i) ingestible particles comprising sodium bicarbonate; wherein the particles are tablets with a thickness of 1 .0 - 2.0 mm and a diameter of 1.0 - 5.0 mm; and wherein the particles contain more than 50 % (w / w) of the sodium bicarbonate; (ii) dry components for preparing a viscous aqueous medium;and optionally (iii) water, wherein the kit is for use in preventing, alleviating or mitigating dystocic labor.

15. A method of preparing a pregnant woman for labor, comprising the step of ingesting a composition as defined in any one of claims 1-12.

16. A method for preventing, alleviating or mitigating labor-induced acidosis and / or acidemia in a pregnant female subject, comprising the step of ingesting a composition as defined in any one of claims 1-12.

17. Use of a composition according to any one of claims 1-11 or a kit according to any one of claims 13-14 to prevent, alleviate or mitigate labor- induced acidosis and / or acidemia in a pregnant woman.

18. Use of a composition according to any one of claims 1-11 or a kit according to any one of claims 13-14 in the preparation of a medicament for preventing, alleviating or mitigating dystocic labor.

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