WO2017176199A1 - Composition de macronutriments à utiliser dans un procédé pour le traitement du diabète gestationnel - Google Patents
Composition de macronutriments à utiliser dans un procédé pour le traitement du diabète gestationnel Download PDFInfo
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- WO2017176199A1 WO2017176199A1 PCT/SE2017/050334 SE2017050334W WO2017176199A1 WO 2017176199 A1 WO2017176199 A1 WO 2017176199A1 SE 2017050334 W SE2017050334 W SE 2017050334W WO 2017176199 A1 WO2017176199 A1 WO 2017176199A1
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- macronutrient composition
- meal
- macronutrient
- composition
- treatment
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- A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- the present invention relates to a macronutrient composition for use in a method for treatment or prevention of gestational diabetes (GDM) in a subject.
- GDM gestational diabetes
- GDM gestational diabetes mellitus
- GDM is a unique form of diabetes because it disappears after delivery of the baby. These different forms of diabetes are treated differently. Insulin is the mainstay of type I diabetes treatment, whereas type II diabetes can be pharmacologically treated with drugs that target cell metabolism (e.g. by metformin). In the case of type II diabetes, treatment usually begins with dietary advice and recommendations for increase of physical activity. GDM patients respond to either metformin or insulin but risks are associated with drug treatment and in the case of GDM one needs to be particularly concerned with potential effects on the developing child. It is clear that there are different forms of diabetes and that treatments of these different forms need to be adapted to the specific type of diabetes.
- GDM there is a lack of effective and harmless treatment.
- GDM recommendations i.e. recommendations on what to eat or not, in contrast to type II diabetic subjects for which recommendations regarding food types are commonly given.
- Hernandez, T.L. et al. presents a research overview regarding nutritional management of GDM, i.e. the use of diet for prevention and treatment of GDM.
- a main conclusion of this research overview is that no particular diet has shown to have any significant effect on prevention or treatment of GDM.
- drug treatments are used in the form of insulin or metformin but there is no generally accepted drug treatment for GDM.
- a purpose of the invention is to provide effective and safe treatment and prevention of GDM using a macronutrient composition.
- the invention concerns a macronutrient composition for use in a method for treatment or prevention of gestational diabetes in a subject, wherein the macronutrient composition is administrated with a time period between administration and a meal ranging from 240 - 15 minutes before said meal, more preferably 60-30 minutes before said meal, wherein the macronutrient composition is administrated orally to the subject at least before one daily meal, preferably before each meal, and wherein the macronutrient composition comprises proteins in the range of 20-60 g/lOOg macronutrient composition, lipids in the range of 5-20 g/100 g macronutrient composition and carbohydrate in the range of 10-50g /100g macronutrient composition.
- the invention also concerns a method of treating or preventing gestational diabetes comprising administering an effective amount of a macronutrient composition to a subject suffering from or posing a particular risk of developing gestational diabetes.
- the invention also concerns a use of a macronutrient composition in a method for treatment or prevention of gestational diabetes in a subject.
- the macronutrient composition may be consumed in various amounts and intake frequencies and still provide for an advantageous effect, the invention focuses on the concept of pre-meal where a small amount of nutrients, typically around 15-20 g, is consumed in addition to standard meals and preferably before each meal. This concept is different from frequency of food intake, which often is referred to in connection with treatment of type II diabetes.
- the macronutrient composition can be consumed three times a day in addition to regular meals, but without specifying exactly how long before a meal the macronutrient composition should be consumed. Preferably, the three occasions when the macronutrient composition is consumed are reasonably evenly distributed over the day.
- administration time between intake of the macronutrient composition and a meal ranges from 240 - 15 minutes before each meal, preferably 120-20 minutes before each meal, more preferably 60-30 minutes before each meal and most preferably around 30 minutes before each meal.
- the macronutrient composition the pre-meal, activates the gastro-intestinal (incretin) system and places the phase of satiety at an earlier time point without adding excessive energy. It also supports the maintenance of balanced post prandial blood glucose levels, being of particular importance to the GDM patient.
- the macronutrient composition for treating GDM can be used for preventing GDM by administering the composition to a subject posing a particular risk of developing GDM. Typically, this would be a mother who has experienced GDM during a previous pregnancy and thus has an increased risk of GDM in her next pregnancy.
- the macronutrient composition, method and use according to the invention thus provides for effective and safe treatment and prevention of GDM.
- GDM gestational diabetes
- Type I is most likely caused by immune-mediated destruction of beta cells whereas Type II relates to insensitivity to insulin.
- Gestational diabetes is unique in that it (1) is reversible (disappears after delivery) and (2) is related to the presence of a placenta and the metabolic adaptations to pregnancy. Furthermore, the diagnosis of gestational diabetes has specific and different diagnostic criteria compared to type II diabetes. The placenta (unique to pregnancy) produces several hormones leading to changes in body metabolism and insulin sensitivity. The situation that GDM is unique from type II diabetes can further be related to specific gene functions.
- One example (in animals) concern elimination of the prolactin (Prl) receptor in pancreatic beta cells.
- Micronutrients are a class of chemical compounds which humans consume in the largest quantities (must be above a threshold amount) and which provide humans with the bulk of energy. There are three primary macronutrients: proteins, fat, and carbohydrates.
- macronutrients are herein defined as proteins, fats, and carbohydrates.
- the macronutrient composition comprises at least proteins, fats, and carbohydrates.
- the method comprises administering the macronutrient composition with a time period between administration of the macronutrient composition, the pre-meal, and meal is ranging from 240 - 15 minutes before each meal, more preferably 60-30 minutes before each meal and most preferably 30 minutes before each meal.
- a meal is herein meant to be a meal having an energy content of at least 1/5 of the recommended daily intake for the actual consumer group, i.e. approximately 400 kcal. In an embodiment, the meal has an energy content of at least 300 kcal.
- pre-meal treatment can be to reduce food intake as well as reduce the need for snacking in between meals.
- Pre-meal treatment leads to a significantly higher postprandial satiety at the onset of the following meal (at time point 0 min, e.g. 30 minutes after pre-meal was given) which reduces meal size and attenuate the following blood sugar response.
- the levels of post-prandial blood glucose (2h-BG) and HbAlc are reduced over time with the consistent use of the pre-meal concept.
- a macronutrient composition used as a pre-meal to treat GDM is likely to affect other components e.g. cholesterol and LDL concentrations as well as CRP, a marker of chronic low grade inflammation.
- the macronutrient composition is administrated orally to the subject at least before one daily meal, preferably before each meal. This will keep the blood sugar levels post meal at a desired level.
- the macronutrient composition is administrated before each meal over a period of time.
- the effect of pre-meal is better if the subject consequently uses pre-meal before each meal, every day, over a period of time. This will provide the subject with consistent long-term benefits.
- the time period during which the macronutrient composition is given may be at least from the day the GDM diagnosis is confirmed, typically between 12 th to 18 th week of pregnancy and on- going until the day of birth.
- the macronutrient composition may also well be given as a prevention diet already at the early days of the confirmed pregnancy. If a patient has one or more risk factors for GDM, treatment with the macronutrient composition can begin already before the conception.
- the macronutrient composition comprises proteins in the range of 20-60 g/lOOg, lipids in the range of 5-20 g/100 g and carbohydrate in the range of 10-50g /100g, as a weigh percent of the total weight of the macronutrient composition.
- the macronutrient composition comprises 20-60 weight-% proteins, 5-20 weight-% lipids and 10-50 weight-% carbohydrates.
- the macronutrient composition comprises egg(s), whey, pea protein and rosaceous plants, such as rose hip and/or apple(s).
- the macronutrient composition comprises pea, whey, chicken egg, rosaceous plants and sugar beet fiber, egg albumin, milk, and eventual flavour, sweetener and colour.
- the macronutrient ingredients are preferably in dry powder form.
- the macronutrient composition is formulated as a dry powder.
- the macronutrient composition is characterized by a low glycemic index.
- a low glycemic index (Gl) is defined as below 55 following internationally accepted technology for measurement. A low-GI food will release glucose more slowly and steadily, which leads to more suitable postprandial (after meal) blood glucose readings. It is also preferred that the macronutrient composition has a low the glycemic load (GL), below 10 following internationally accepted standard calculation.
- the macronutrient composition is dissolved in water, other liquids or semi liquids and administrated as a pre-meal drink.
- the macronutrient composition is formulated to provide an energy value ranging between 60 - 200 kcal, more preferably 70 - 130 kcal/g.
- the macronutrient composition further comprises micro nutrients and/or trace elements as natural constituents.
- the macronutrient composition is enriched with micro nutrients and/or trace elements.
- the macronutrient composition is administered in an amount of 10-30 g, preferably 12-25 g, more preferably 14-20 g per serving.
- the amount per serving of the macronutrient composition is ca 18 g.
- Such a serving can include 7.5 g protein, 1.5 g fat (a mix of saturated and unsaturated fat), 1 g fiber and 4 g carbohydrates, which provides approximately 70 kcal energy. It can also include around 1 g of micronutrients (minerals and vitamins) and water.
- the gestational diabetes is defined as elevated fasting glucose values or pathological test results following an oral glucose tolerance tests or standardized meals.
- subjects with gestational diabetes are treated with the macronutrient composition.
- subjects at risk to develop gestational diabetes are treated with the macronutrient composition.
- the efficacy of the macro-nutrient pre-meal method is monitored by measurements of glucose, insulin, GLP-1 and/or GLP-2.
- the blend of nutrients in the pre-meal ideally includes proteins from different sources since the kinetics and bioavailability differs as well as the amino acid profile.
- Whey protein is the fastest (impact on insulin release) and pea protein is probably the most satiating. Fibers in the pre-meal also stimulate the feeling of satiety, as well as a feeling of fullness in the stomach.
- the pre-meal also has a low Glycemic Index and contain few calories. Since users are likely to reduce their meal sizes it is an advantage that the pre-meal mix has a high content of essential nutrients including all essential amino acids and Omega 3 and 6 fatty acids in a preferred balance.
- pre-meal is used for the macronutrient composition of the invention
- pre-meal concept is used for the macronutrient composition of the invention being administrated at a predetermined time prior to a meal.
- the invention also concerns a method of treating gestational diabetes comprising administering an effective amount of a macronutrient composition to a subject suffering from gestational diabetes.
- the method comprises administering the macronutrient composition with a time period between the administration of the macronutrient composition, the pre-meal, and a meal ranging from 240 - 15 minutes before each meal, more preferably 60-30 minutes before each main meal. This time range allows the macronutrient composition to achieve the optimal effect on satiety and attenuate the following blood sugar response.
- the method of treating or preventing gestational diabetes comprises administering an effective amount of a macronutrient composition to a subject suffering from or posing a particular risk of developing gestational diabetes.
- the method comprises administrating the macronutrient composition orally to the subject at least before one daily meal, preferably before each meal.
- gestational diabetes is being defined as elevated fasting glucose values or pathological test results following an oral glucose tolerance tests or standardized meals.
- the method comprises measuring levels of certain components in blood, wherein the components are chosen from the group including GLP-1, GLP-2, insulin, HblAC, fatty acid and cholesterol containing components, such as to monitor the effect of the treatment.
- the administration scheme of the pre-meal may be determined based on the levels measured.
- the method comprises the step of dissolving the macronutrient composition in water, other liquids or semi liquids and administrating the macronutrient composition as a pre-meal drink.
- the method may comprise preparing a macronutrient composition comprising eggs, whey, pea protein and rosaceous plants in dry powder form.
- the invention also concerns the use of a macronutrient composition in a method for treatment or prevention of gestational diabetes in a subject.
- Figure 1 exemplifies pre-meal concept used in treatment of GDM.
- the present inventors have found that patients with gestational diabetes react significantly to a method of treatment using the pre-meal concept, i.e. eating a macronutrient composition prior to a meal.
- the pre-meal macronutrient composition used consisted of a mix of high quality macronutrients given to patients 30 min before each meal.
- the ingestion of a low calorie composition of macronutrients with a low glycaemic index before regular meals resulted in an improvement of the metabolic situation for women with diagnosed gestational diabetes (GDM).
- Gestational diabetes is usually diagnosed relatively late during pregnancy.
- Figure 1 shows a time line of the first 1, second 2 and third 3 trimester of a pregnancy.
- the schematic Figure 1 indicates a time point 4 of GDM diagnosis; second trimester.
- Point 5 indicates the beginning of the pregnancy.
- Pre-meal treatment is initiated and the treatment goes on until delivery.
- the Pre-meal concept involves the intake of a defined macronutrient composition before each regular meal; breakfast 6, lunch 7 and dinner 8, shown on the lower bar that represents one day.
- a suitable pre-meal schedule during one day is illustrated in the lower bar: arrows represent the pre-meal 30 minutes before breakfast 6, lunch 7 and dinner 8.
- pre-meal treatment can begin already at the start of or before pregnancy 5 and go on throughout the entire pregnancy. This is suitable if the woman has suffered from GDM during a previous pregnancy.
- Example 1 Example of a macro nutrient composition that can be used to practice the present invention
- Indevex Nutrientshake is a commercially available dry powder formulation (Indevex AB (publ), Sweden; www.indevex.com).
- the Indevex Nutrientshake is based on NGC Premix consisting of natural macronutrient whole food ingredients (pea, whey, chicken egg, rosaceous plants and sugar beet fiber), egg albumin, milk, and eventual flavour, sweetener and colour.
- Indevex Nutrientshake comprises proteins from whey (milk), egg and peas. The three sources of protein covers approximately 1/3 of the body's daily need for all essential amino acids (Indevex Nutrientshake has a high amino acid score according to WHO criteria) which is important in building and maintaining muscle mass.
- Indevex Nutrientshake contains carbohydrates that are slowly digested. Indevex Nutrientshake contains the two important essential fatty acids, Omega 3 and 6, both polyunsaturated fatty acids (PUFAs). These contain linoleic acid (LA) and alpha-linoleic acid (ALA), widely distributed in plant oils.
- LA linoleic acid
- ALA alpha-linoleic acid
- the human body has a limited ability to convert ALA into the longer-chain Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which also can be obtained from fish.
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the balance between Omega 3 and 6 is vital for health.
- the Omega 3 and 6 fatty acids ratio present in the product is within the ratio 1:2 - 1:4. Rosaceous plants are naturally rich in vitamins, especially vitamin C which is an important antioxidant.
- Indevex Nutrientshake contains both water-soluble and water-insoluble dietary fibres.
- the composition comprises fat, carbohydrates, proteins, vitamins and minerals, wherein the carbohydrates are derived from foodstuffs having a low glycemic index; and wherein the macronutrient composition comprises fat, carbohydrates, proteins, vitamins and minerals present in the form of 10-20% whole eggs, 10-25% whey, 15-30% yellow peas, 4- 15% egg albumen and 15-40% rosaceous plants, each as a weight percent of the macronutrient composition.
- a serving of Indevex Nutrientshake in the form of a dry powder mix shake product (18 grams) includes 15 grams of the NGC Premix ingredient, including and providing approximately 7.5 g protein, 1.5 g fat (a mix of saturated and unsaturated fat), 1 g fiber and 4 g carbohydrates, which provides approximately 70 kcal energy.
- the 15 g of NGC Premix includes also around 1 g of micronutrients (minerals and vitamins) and water.
- a serving of Indevex Nutrientshake contains ingredients added to improve taste.
- the dry powder is intended to be mixed by shaking with 150 ml cold drinking water (and this was done in the experiments described in this document).
- the GL value of this pre-meal macronutrient composition is less than 10.
- a macronutrient composition mix is given in detail herein.
- Other macronutrient compositions that also fulfil e.g. low calorie and low glycemic index requirements, preferably a Gl below 55, may alternatively be used.
- OGTT oral glucose tolerance test
- the pre-meal concept treatment administrating the macronutrient composition to the patient prior to meals, will begin at the first instance following the diagnosis of GDM 4.
- the recommended treatment schedule will be approximately 30 minutes before each meal i.e. a macronutrient pre-meal before breakfast 6, lunch 7 and dinner 8.
- the pre-meal concept treatment will begin when pregnancy has first been identified 5 and this is of particular relevance for patients with an elevated GDM risk e.g. those who have previously had GDM.
- OGTT oral glucose tolerance tests
- a patient was tested using a standardized oral glucose tolerance tests (OGTT) by drinking 200 ml water containing 75 g glucose, i.e. a glucose solution. Insulin was measured using a radioimmunoassay in blood samples obtained at the time points indicated. OGTT was carried out in the morning before breakfast and was first carried out without pre-meal, four days later OGTT was repeated with pre-meal (Indevex Nutrientshake). The control situation consisted of 200 ml of water. It can be observed that pre-meal treatment given 30 minutes before the OGTT increased levels of insulin.
- the pre-meal macronutrient composition used was Indevex Nutrientshake as described in Example 1. In similar procedures one can use other read-outs, e.g. GLP-1 to monitor the biological activity of pre-meal treatments.
- Example 4 Effect of a macronutrient pre-meal in gestational diabetes.
- a first group the Treatment group, received pre-meal concept treatment using the composition described in Example 1.
- a second group, the Control group received comparative pre-meal treatment based on milk powder and having a similar caloric content as the pre-meal of the Treatment group.
- the pre-meals were given to patients 30 min before each meal. The treatment was continued for nine weeks (average 65 days) until delivery. Levels of fasting blood glucose and two-hour postprandial blood glucose (two hours after a standardized meal) were determined before starting the treatment as well as after treatment (after nine weeks). The results are shown in Table 2.
- pre-meal concept treatment significantly improved glucose tolerance following a standardized meal in the Treatment group. This follows from the observation that the macro-nutrient pre-meal treatment significantly reduced the 2h post prandial glucose level compared to the level before treatment (the mean value was reduced from 9.25 to 6.06). The corresponding level for the Control group might also have been somewhat reduced (from 8.86 to 7.12) but this difference is not significant.
- the experiment demonstrates that the macronutrient pre-meal treatment is beneficial for the control of postprandial blood glucose in patients with gestational diabetes.
- Patients hospital days, differences of delivery mode and birth weight were also compared.
- the fasting blood sugar and 2 hour postprandial sugar before delivery was significantly lower in the intervention/treatment group, p ⁇ 0,05.
- the time for delivery and birth weight was not different between the groups.
- the study suggests that macronutrient pre-meal treatments can be routinely used in patients with gestational diabetes as a valuable nutritional intervention.
- Example 5 In this example a typical patient is described that is treated with the pre-meal concept.
- a woman age 32 was found to have a fasting blood sugar value of 8 mmol/l that was detected on two different occasions, when subjected to the standard oral glucose tolerance test her 2h value was 10 mmol/l.
- GDM gestational diabetes mellitus
- the patient was referred to a maternal care unit, specialized in the care of GDM.
- the patient was found to be pregnant in the late second trimester, slightly over weight and had a normal blood pressure. The pregnancy was found to proceed normally and there were no signs of any other pathologies than GDM.
- the patient did not report any allergies or intolerance to lactate or gluten.
- the patient was given life style advice consisting of dietary recommendation and encouragement of increased physical activity.
- the patient was also instructed to adhere to the pre-meal concept and she was given a pre-meal composition as described in Example 1 to be taken three times per day, 30 minutes before each meal until the time of delivery. Repeated check-ups of the patients found near to normal blood glucose values and she delivered a normal baby within the predicted time for delivery.
- Example 6 In this example a typical patient is described that is treated with the pre-meal concept.
- GDM gestational diabetes
- She blood sugar was found to within the normal range and this was also the case with the oral glucose tolerance test. She has no other symptoms of disease and did not report any past disorders with the exception of GDM, she was not allergic, nor lactate or gluten intolerant. Because of the increased risk to develop GDM she was given pre-meal treatment as in Example 5. Evaluation of her health status showed that she did not develop GDM and that she later gave birth to a normal child.
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Abstract
La présente invention concerne une composition de macronutriments à utiliser dans un procédé pour le traitement ou la prévention du diabète gestationnel chez un sujet et un procédé de traitement du diabète gestationnel consistant à administrer une quantité efficace d'une composition de macronutriments à un sujet souffrant de diabète gestationnel ou présentant un risque particulier de développer un diabète gestationnel.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111000223A (zh) * | 2019-12-17 | 2020-04-14 | 北京惠爱惠远国际健康管理有限公司 | 妊娠糖尿病孕中晚期控糖营养餐制备方法 |
CN112890177A (zh) * | 2021-02-24 | 2021-06-04 | 云南屯屯麦生物技术研究有限公司 | 一种用于降低妊娠期餐后血糖水平的组合物及其制备方法 |
EP3809880A4 (fr) * | 2018-06-22 | 2022-03-23 | Fonterra Co-Operative Group Limited | Utilisation de lipides polaires pour traiter ou prévenir le diabète sucré gestationnel |
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EP2011506A1 (fr) * | 2007-07-05 | 2009-01-07 | Nestec S.A. | Supplémentation de régime maternel |
WO2016020489A1 (fr) * | 2014-08-08 | 2016-02-11 | Nestec S.A. | Vitamine b2 pour diabète gestationnel |
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2016
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EP2011506A1 (fr) * | 2007-07-05 | 2009-01-07 | Nestec S.A. | Supplémentation de régime maternel |
WO2016020489A1 (fr) * | 2014-08-08 | 2016-02-11 | Nestec S.A. | Vitamine b2 pour diabète gestationnel |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3809880A4 (fr) * | 2018-06-22 | 2022-03-23 | Fonterra Co-Operative Group Limited | Utilisation de lipides polaires pour traiter ou prévenir le diabète sucré gestationnel |
CN111000223A (zh) * | 2019-12-17 | 2020-04-14 | 北京惠爱惠远国际健康管理有限公司 | 妊娠糖尿病孕中晚期控糖营养餐制备方法 |
CN112890177A (zh) * | 2021-02-24 | 2021-06-04 | 云南屯屯麦生物技术研究有限公司 | 一种用于降低妊娠期餐后血糖水平的组合物及其制备方法 |
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