A composition having a lactagogue effect and use thereof

Abstract

The application discloses a composition with lactation promoting effect and application thereof. Researches of the application show that oyster peptide can promote mammary gland development, improve lactation related hormones and promote lactation. Meanwhile, the application provides a composition with lactation promoting effect, which comprises oyster peptide, astragalus polysaccharide and soybean isoflavone. Researches show that the composition of oyster peptide, astragalus polysaccharide and soybean isoflavone can improve lactation performance of mammals and increase lactation yield. The oyster peptide has a synergistic effect when being used in combination with astragalus polysaccharide and soybean isoflavone, and can promote lactation and mammary gland development, and improve lactation related hormones. The composition is prepared into oyster peptide lactation promoting granules, and the components are green, natural, safe, nutritious, non-toxic and non-side effect, can effectively increase the hourly lactation yield of postpartum lactation deficient mice, serum and mammary gland tissue PRL, PRLR level and mammary gland organ index, and has an improving effect on postpartum lactation deficiency.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine. More particularly, it relates to a composition with lactation-promoting effect and its application. BACKGROUND

[0002] Postpartum lack of milk is a common obstetric disease, which means that the puerpera has less milk or no milk during lactation period, which cannot meet the feeding needs of infants. According to traditional Chinese medicine theory, postpartum lack of milk is divided into three types: deficiency of qi and blood, liver stagnation and phlegm turbidity obstruction. The treatment method of "replenishing deficiency and dispersing excess" has a long history. Modern medicine believes that due to external or internal factors, the hypothalamus can inhibit the synthesis of prolactin (PRL) by secreting dopamine (DA) and other prolactin inhibiting hormones into the blood circulation, thereby inhibiting the secretion of prolactin (PRL) in the body, which can inhibit the secretion of milk. These factors include environmental factors such as environmental stress; internal factors such as insufficient development of mammary glands; dietary structure such as insufficient nutrition, etc. Nutrients are the material basis of milk, and the mother is the source of milk nutrients. If the mother's nutritional intake is insufficient, the quality and quantity of milk will be affected, so the postpartum dietary nutrition supplement is crucial to the recovery of the mother and the formation of breast milk.

[0003] At present, most of the treatments for postpartum lack of milk are to use traditional Chinese medicine or food-medicine extract, or to improve the dietary nutrition of puerpera and use plant estrogen lactation effect to improve symptoms. Because most of the lactation products on the market have different degrees of toxic and side effects, natural lactation products have attracted much attention. The lactation traditional Chinese medicine reported in the prior art uses multiple traditional Chinese medicine ingredients, such as Sappan, Angelica, Poria cocos, Baizhi, Huangling, Jinyinhua, Maitong, Tongcao, Chenpi, Chuanxiong, Honghua, Chuan-shanying, Wangbuliuxing, Huangqi or Maidou, Wangbuliuxing, Longgu, Chuan-shanying, Zihuche, Jinyinhua, etc. They are used to regulate lactation from multiple aspects. Although pure traditional Chinese medicine components are green and non-toxic, their effects are slow, and their efficacy needs to be improved. It is also troublesome to take decoction, and the cost is high. At present, there are still few non-traditional Chinese medicine products that can be directly used to promote lactation and mammary gland development, improve lactation-related hormones, and therefore the development of natural lactation products provides a green and safe lactation dietary supplement for puerpera with postpartum lack of milk. SUMMARY

[0004] The technical problem to be solved by the present application is to overcome the defects and deficiencies of the above-mentioned problems, and to provide a composition with lactation-promoting effect and its application.

[0005] The first object of the present application is to provide the application of oyster peptide in promoting mammary gland development, improving lactation-related hormones, promoting lactation or in preparing a drug for lack of milk.

[0006] The second object of the present application is to provide a composition with lactation-promoting effect.

[0007] A third object of the present application is to provide the use of the composition.

[0008] A fourth object of the present application is to provide an oyster peptide granule powder having a lactogenic effect.

[0009] The above objects of the present application are achieved by the following technical solutions.

[0010] Oyster peptide is rich in nutrients and is known as "marine milk". The present application shows that oyster hydrolyzed peptide has an improving effect on the lactation function of postpartum lactation-deficient rats, significantly up-regulates the expression level of PRL, PRLR genes and milk protein synthesis genes of human mammary epithelial cells, and can promote mammary gland development, improve lactation-related hormones and promote lactation. Therefore, the present application first provides the use of oyster peptide in promoting mammary gland development, improving lactation-related hormones, promoting lactation or in preparing a lactation-deficiency drug.

[0011] The present application also provides a composition having a lactogenic effect, comprising oyster peptide, astragalus polysaccharide and soybean isoflavone.

[0012] Astragalus polysaccharide is a plant extract with medicinal and edible properties. According to traditional Chinese medicine theory, it has the effects of tonifying qi and nourishing blood and has certain curative effect on postpartum qi-blood conditioning of puerpera. Soybean isoflavone is a plant estrogen similar in structure to mammalian estradiol, and this estrogen can promote the secretion of lactation-related hormones and has a positive effect on the treatment of breast cancer and the prevention of complications after menopause. The present application shows that the combination of oyster peptide, astragalus polysaccharide and soybean isoflavone can improve the lactation performance of mammals and increase the lactation yield. It is also shown that the combination of oyster peptide, astragalus polysaccharide and soybean isoflavone has a synergistic effect, which can promote lactation and mammary gland development, improve lactation-related hormones, and achieve similar effects to pure oyster peptide at a low dosage, thereby effectively reducing the dosage while achieving the same effect.

[0013] Preferably, the mass ratio of the oyster peptide, astragalus polysaccharide and soybean isoflavone is 10-12:1-5:0.5-2.

[0014] More preferably, the mass ratio of the oyster peptide, astragalus polysaccharide and soybean isoflavone is 12:5:1.

[0015] The present application provides the use of the oyster peptide composition having a lactogenic effect in promoting mammary gland development, improving lactation-related hormones, promoting lactation or in preparing a lactation-deficiency drug.

[0016] In particular, the oyster peptide, astragalus polysaccharide and soybean isoflavone used in the present application can be directly used in commercially available products, and the oyster peptide can also be prepared by conventional enzymatic preparation of peptides in the art.

[0017] More preferably, the method for preparing oyster peptide is prepared according to the reference: Changge, oyster protein hydrolysis product anti-fatigue effect research and new product development[D]. Zhanjiang, Guangdong Ocean University, 2016.

[0018] The present application provides a kind of oyster peptide granules of lactation-promoting effect, comprising the following components:

[0019] Main materials: oyster peptide, astragalus polysaccharide, soybean isoflavone;

[0020] Auxiliary materials: mannitol, lactose;

[0021] Flavoring agent: ginger powder, papaya powder, brown sugar.

[0022] In particular, the auxiliary materials and flavoring agents used in the present application are used to mask the sea smell of oyster raw materials, and are not limited to the auxiliary materials and flavoring agents used in the present application. The granule forming rate of the granules prepared by using the specific ratio of auxiliary materials and flavoring agents in the present application is higher, the taste is better, and the effect is best.

[0023] Preferably, the mass ratio of the auxiliary materials to the main materials is 1:1-2, and the mass ratio of the auxiliary materials mannitol and lactose is 1-2:1.

[0024] Preferably, the mass ratio of the flavoring agent brown sugar: papaya powder: ginger powder is 4-6:1-1.5:1-1.5, and the amount is 15-25%.

[0025] More preferably, the mass ratio of the flavoring agent brown sugar: papaya powder: ginger powder is 5:1:1.

[0026] More preferably, the oyster peptide granules comprise the following raw materials in the following mass percentage: oyster peptide 20%, astragalus polysaccharide 8.5%, soybean isoflavone 1.7%, ginger powder 2.1%, papaya powder 2.1%, brown sugar 10.7%, mannitol 36.2%, and lactose 18.1%.

[0027] The present application provides a preparation method of oyster peptide granules, which comprises the following steps: mixing and stirring the components of the oyster peptide granules to obtain a mixture; adding edible alcohol to the mixture to obtain a soft material; sieving the soft material; drying the soft material at 55-60°C for 2-5h; sieving and arranging the soft material to obtain the oyster peptide granules.

[0028] Preferably, 10%-12% edible alcohol with a concentration of 75%-95% is used.

[0029] The present application has the following beneficial effects:

[0030] The research of the present application shows that oyster peptide can promote breast development, improve lactation-related hormones, and promote lactation; at the same time, the research shows that the composition composed of oyster peptide, astragalus polysaccharide, and soybean isoflavone has a lactation-promoting effect, can significantly improve the lactation amount of the lactating mother mouse, increase the mammary organ index of the mother mouse, significantly improve the PRL and PRLR levels in the serum and mammary tissue of the mother mouse, and improve the mammary structure of the mother mouse; the compatibility of oyster peptide, astragalus polysaccharide, and soybean isoflavone can achieve a synergistic effect, and the composition can achieve an effect comparable to that of the pure oyster peptide group and the positive control blood-enriching and milk-producing granules group, thereby providing a theoretical reference for the development of postpartum lactation-promoting products.

[0031] At the same time, the oyster peptide lactation-promoting granule preparation prepared by the present application can significantly improve the lactation amount of the lactating mother mouse, reduce the weight loss of the mother mouse, significantly increase the mammary organ index of the mother mouse, significantly improve the PRL and PRLR levels in the serum and mammary tissue of the mother mouse, increase the mammary gland alveoli of the mother mouse, and enlarge and proliferate the mammary gland alveoli, thereby indicating that the oyster peptide lactation-promoting granule preparation can improve postpartum hypogalactia, promote breast development, improve lactation-related hormones, and promote lactation. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 Effect diagram of weight loss of mother mouse and weight gain of baby mouse;

[0033] Figure 2 Histological morphology diagram of mammary glands of mother mouse in each group (HE, x200);

[0034] Figure 3 Comparison result diagram of PRL, PRLR, and DA levels in serum of mother mouse in each group;

[0035] Figure 4 Comparison result diagram of PRL and PRLR levels in mammary tissue of mother mouse in each group;

[0036] Figure 5 Influence result diagram of auxiliary material and main material ratio, flavoring agent addition amount, and ethanol concentration on comprehensive score;

[0037] Figure 6 Three-dimensional response surface diagram of interaction of each influencing factor;

[0038] Figure 7 Statistical diagram of weight loss of mother mouse;

[0039] Figure 8 Statistical diagram of mammary organ index;

[0040] Figure 9 Statistical diagram of PRL and PRLR levels in serum and mammary tissue;

[0041] Note: B group in the figure refers to the blank group; M group refers to the model group; P group refers to the positive control group (Buxie Shengru Granules group); OH group refers to the oyster peptide group; LF group refers to the composition (oyster peptide, astragalus polysaccharide, soybean isoflavone) low dose group; HF group refers to the composition (oyster peptide, astragalus polysaccharide, soybean isoflavone) high dose group; Different lower case letters indicate significant differences between groups (P<0.05). DETAILED DESCRIPTION

[0042] The present application will be further described below in conjunction with the drawings and specific examples of the present application, but the examples do not make any form of limitation to the present application. Unless specifically stated, the reagents, methods and equipment used in the present application are conventional reagents, methods and equipment in the technical field.

[0043] Unless specifically stated, the reagents and materials used in the following examples are commercially available.

[0044] The astragalus polysaccharide and soybean isoflavone used in the present application are purchased from Shaanxi Haoyang Biological Technology Co., Ltd., and the purity of astragalus polysaccharide is 55.23% and the purity of soybean isoflavone is 40.15%.

[0045] Example 1 Oyster peptide composition

[0046] (1) Preparation of oyster peptide

[0047] The method for preparing oyster peptide in this example is referred to: Chang G. Anti-fatigue effect of oyster proteinase hydrolysate and new product research and development [D]. Zhanjiang, Guangdong Ocean University, 2016. The oyster peptide used therein can be directly obtained from commercially available products or prepared by conventional enzymatic preparation of peptides in the art.

[0048] The specific method is as follows: fresh oyster meat is washed clean, drained, distilled water is added according to the material to water ratio of 1:3, homogenized, the pH is adjusted to neutral, animal proteinase is added, the amount of animal proteinase added is 1000 U / g, and the enzyme is placed in a water bath for enzymolysis, the enzymolysis temperature is 53℃, 4h, after the enzymolysis is completed, the supernatant is obtained by centrifugation, the centrifugation condition is 12000r / min, 20min, the supernatant is freeze-dried to obtain oyster peptide powder for dry preservation.

[0049] (2) Setting of experimental groups

[0050] SPF grade KM mice (7-8 weeks, male 42~45g, female 35~38g) were selected for the experiment, and the feeding conditions were as follows: humidity (55%±10%), temperature (24±2 ℃), light / dark treatment cycle 12 h, and the mice could freely obtain water and maintain feed. After one week of adaptive temporary feeding, female mice were caged with male mice at a ratio of 2:1 for mating, and continuous caging was performed until sperm was observed in the vaginal smear of the female mice. The successfully fertilized female mice were separated from the male mice, and when the female mice were 20 days pregnant, they were adjusted to one pregnant mouse per cage, and delivery was awaited.

[0051] Forty-eight female mice with a difference of no more than 24 h in the time of giving birth were taken as experimental objects, and were randomly divided into a blank group, a model group, a positive control group, a pure oyster peptide group, a low-dose oyster peptide combination group, and a high-dose oyster peptide combination group; 8 mice per group, methimazole was used for modeling, and blood supplementing and milk producing granules were used as a positive control, and the actual gavage dose was calculated according to the body weight of each mouse (according to the effective measurement standard).

[0052] The blank group (group B): distilled water was gavaged, 5 mL / kg, twice a day;

[0053] The model group (group M): 8 mg / kg of methimazole solution was gavaged at 9 am every day, and 5 mL / kg of distilled water was gavaged at 3 pm every day;

[0054] The positive control group (group P): 8 mg / kg of methimazole solution was gavaged at 9 am every day, and 4272 mg / kg of blood supplementing and milk producing granules was gavaged at 3 pm every day;

[0055] The pure oyster peptide group (group OH): 8 mg / kg of methimazole solution was gavaged at 9 am every day, and 2000 mg / kg of oyster peptide was gavaged at 3 pm every day;

[0056] The low-dose oyster peptide combination group (group LF): 8 mg / kg of methimazole solution was gavaged at 9 am every day, and 500 mg / kg of oyster peptide combination was gavaged at 3 pm every day, wherein the oyster peptide combination contains oyster peptide, astragalus polysaccharide, and soybean isoflavone, and the mass ratio is 12:5:1;

[0057] The high-dose oyster peptide combination group (group HF): 8 mg / kg of methimazole solution was gavaged at 9 am every day, and 2000 mg / kg of oyster peptide combination was gavaged at 3 pm every day, wherein the oyster peptide combination contains oyster peptide, astragalus polysaccharide, and soybean isoflavone, and the mass ratio is 12:5:1;

[0058] The milk secretion amount of the female mice per hour, the weight loss of the female mice per day, and the blood and mammary gland tissue of the female mice were recorded after 10 days, and the PRL and PRLR levels in the serum and mammary gland tissue of the female mice were determined.

[0059] The effects of oyster peptide and each treatment group on the body weight of postpartum hypogalactia mother mice and the body weight of baby mice were as follows Figure 1 It was known that the body weight reduction of mother mice in M group was significantly increased compared with B group P <0.05), and the body weight of mother mice in each treatment group was obviously recovered compared with M group P <0.05). The net weight gain of baby mice in M group was significantly different from that in B group P <0.05); the net weight gain of baby mice in high and low dose groups of the composition was 25% more than that in M group, and the difference was significant P <0.05), and the difference was not significant compared with P group P >0.05).

[0060] The effects of oyster peptide and each treatment group on the milk secretion of postpartum hypogalactia mother mice were as follows P <0.05), indicating that the postpartum hypogalactia mouse model was successfully established. Compared with M group, the hourly milk secretion of mother mice in P group, LF group and HF group was increased by 41.98%, 42.75% and 46.56% respectively on the 5th day, and the difference was significant P <0.05); from the 6th day, the hourly milk secretion of mother mice in each treatment group was obviously higher than that in M group P <0.05), and there was no significant difference between LF group and HF group and P group and OH group P <0.05).

[0061] Table 1 Hourly milk secretion of mother mice

[0062]

[0063] The mammary gland organ index was as shown in Table 2. The mammary gland organ index of mother mice in M group was obviously reduced compared with B group P <0.05); and P group, OH group and high and low dose groups of the composition had an obvious recovery trend compared with M group P <0.05), and there was no significant difference between B group, P group, OH group and high and low dose groups of the composition P >0.05).

[0064] Table 2 Mammary gland organ index

[0065]

[0066] The effects of oyster peptide and each treatment group on the structure of mammary gland tissue of postpartum hypogalactia mother mice were as follows Figure 2As shown, in group B, the mammary alveoli of the mother mice were larger, with regular and rounded shapes, and visible secretions. In group M, the mammary alveoli of the mother mice were irregular in shape, the mammary tissue was severely atrophied, and the interlobular septa were thickened. Compared with group M, the mammary alveoli of the mother mice in groups P and OH were larger and more regular, and visible secretions were visible. The area of ​​mammary lobules in the high and low dose groups of the composition was significantly larger than that in group M, and the alveoli were regular. In particular, compared with groups P and OH, the mammary tissue in group HF contained a large amount of secretions, and the mammary lobules showed a tendency to expand outward.

[0067] Results of oyster peptide and various treatment groups on serum and mammary tissue PRL, PRLR, and DA levels in postpartum lactation-deficient mice are as follows: Figure 3 As shown, compared with group B, the serum PRL and PRLR levels of female mice in group M were significantly decreased; compared with group M, the PRL and PRLR levels in groups P and OH were significantly increased. P >0.05); the high and low dose groups of the composition significantly increased PRL, and the high dose group significantly increased PRLR ( P The difference between the group >0.05 and the P group and the OH group was not significant. P >0.05%, the low-dose group of the composition did not show a significant increase in PRLR levels ( P >0.05). Serum DA results indicate ( Figure 3 Serum DA levels in group M were significantly higher than those in group B. P >0.05), while compared with group M, the DA levels in each dosage group of the composition were significantly reduced ( P >0.05) and there was no significant difference compared with the P group and the OH group ( P >0.05).

[0068] Depend on Figure 4 It can be seen that the levels of PRL and PRLR in the breast tissue of group M were significantly lower than those in group B. P >0.05), while the levels of PRL and PRLR in the P group and OH, and the high and low dose groups of the composition were significantly higher than those in the M group ( P >0.05%. There was no significant difference between the high and low dose groups of the composition and the P and OH groups. P >0.05), and the PRL level in breast tissue of the HF group was not significantly different from that of the B group ( P >0.05).

[0069] In summary, the dosage of the composition group adopted by the present application is significantly lower than the dosage of the positive control Buxie Shengru granules group, and the improvement effect is comparable, and it is shown that the pure oyster peptide group can promote mammary gland development, improve lactation-related hormones, and promote lactation; and only 60%-66.6% of oyster peptides by weight are used in the composition of different dosages, and the improvement effect is comparable to that of the pure oyster peptide group and the positive control Buxie Shengru granules group, which shows that Astragalus polysaccharides and soybean isoflavones can better synergize with oyster peptides to significantly improve the lactation of lactating mice, increase the mammary organ index of mice, increase the PRL and PRLR levels in the serum and mammary tissue of mice, and improve the mammary structure of mice, while achieving the same effect, the dosage can be effectively reduced; the combination of oyster peptides, Astragalus polysaccharides and soybean isoflavones can achieve a synergistic effect, which provides a theoretical reference for the development of postpartum lactation products.

[0070] Example 2 Oyster peptide lactation granule

[0071] On the basis of the research in Example 1, oyster peptides, Astragalus polysaccharides and soybean isoflavones are used as the main active ingredients to prepare oyster peptide granule, and the main material of the granule is oyster peptides, Astragalus polysaccharides and soybean isoflavones, the auxiliary material is mannitol and lactose, and the flavoring agent is ginger powder, papaya powder and brown sugar.

[0072] The preparation method of the oyster peptide lactation granule is as follows: the components of the oyster peptide lactation granule are mixed and stirred uniformly, and then sieved through 10-14 mesh and 80 mesh sieves; then edible ethanol is used to prepare a soft material; the sieved material is dried at 55-60°C for 4h, sieved and finished to obtain the oyster peptide lactation granule.

[0073] It is found through the pre-experiment of the present application that when the proportion of the auxiliary materials mannitol and lactose is 2:1, the proportion of the main materials oyster peptides:Astragalus polysaccharides:soybean isoflavones is 12:5:1, the concentration of ethanol is 75%, the amount is 10%-12%, the proportion of the flavoring agent brown sugar:papaya powder:ginger powder is 5:1:1, and the amount is 15%, the granule forming rate is higher and the taste is better.

[0074] Example 3 Optimization of oyster peptide lactation granule

[0075] 1. Single factor test

[0076] (1) Investigation of the proportion of main materials and auxiliary materials

[0077] According to the pre-experiment of Example 2, the mannitol and lactose ratio is 2:1, the main material oyster peptide: astragalus polysaccharide: soy isoflavone = 12:5:1, the ethanol concentration is 75%, the dosage is 10%-12%, the flavoring agent brown sugar: papaya powder: ginger powder = 5:1:1, the dosage is 15%, the single factor test is carried out. According to the comprehensive index evaluation result, the different proportions of auxiliary materials: main materials = 2:1, 1.5:1, 1:1, 1:1.5, 1:2 are granulated, the granulation process is observed, and the four key indicators of forming rate, angle of repose, moisture and dissolution rate are measured, and the comprehensive scores are compared.

[0078] The comprehensive score formula is:

[0079]

[0080] (2) Investigation of ethanol concentration

[0081] The mannitol and lactose ratio is 2:1, the main material oyster: astragalus polysaccharide: soy isoflavone = 12:5:1, the auxiliary material: main material = 1:1, the flavoring agent brown sugar: papaya powder: ginger powder = 5:1:1, the dosage is 15%, according to the comprehensive index evaluation result, the ethanol concentration is 55%, 65%, 75%, 85%, 95%, the dosage is 10%-12%, granulation is carried out, the granulation process is observed, and the four key indicators of forming rate, angle of repose, moisture and dissolution are measured, and the comprehensive scores are compared.

[0082] (3) Investigation of flavoring agent ratio

[0083] The mannitol and lactose ratio is 2:1, the main material oyster: astragalus polysaccharide: soy isoflavone = 12:5:1, the auxiliary material: main material = 1:1, the ethanol concentration is 75%, the dosage is 10%-12%, according to the comprehensive index evaluation result, the flavoring agent brown sugar: papaya powder: ginger powder = 5:1:1, the dosage is 5%, 10%, 15%, 20%, 25%, granulation is carried out, the granulation process is observed, and the four key indicators of forming rate, angle of repose, moisture and dissolution are measured, and the comprehensive scores are compared.

[0084] Tukey's test in single factor variance analysis is used to test significance, p <0.05 has significance. Among them p <0.05, p <0.01 compared with the model group; p <0.05, p <0.01 compared with the blank group.

[0085] The single factor experiment results are as follows Figure 5It was found that the comprehensive score was higher and the difference was not big when the ratio of auxiliary material to main material was 1:1~2, the flavoring agent addition was 15%~25%, and the ethanol concentration was 75%~95%, and the molding rate, moisture content, fluidity, and dissolution rate all met the requirements of production process and detection standards.

[0086] 2.Response surface experiment

[0087] Based on the single factor experiment, three-factor and three-level design was carried out, which was shown in Table 3. Design-Expert 8.0 software was used to take auxiliary material: main material (A), flavoring agent ratio (B), and ethanol concentration (C) as independent variables, and the comprehensive score (Y) of particle molding rate (Y1), angle of repose (Y2), moisture content (Y3), and dissolution rate (Y4) as response value for model fitting, and the results were shown in Table 4.

[0088] Table 3 Response surface factor level table

[0089]

[0090] Table 4 Response surface design and results

[0091]

[0092] Design-Expert 8.0 software was used to process data, and the binary multiple regression simulation equation between response value and independent variables A, B, and C was obtained: Y = 83.74 + 0.58A - 0.51B + 0.20C - 1.99AB - 0.26AC + 1.96BC - 2.52A 2 + 1.87B 2 - 1.55C 2 Variance analysis of the above regression model was carried out. The results were shown in Table 5. It was found from the table that the effect of auxiliary material to main material ratio on response value was the biggest, P = 0.0001 < 0.01, which indicated that the model established under the formula was extremely significant. The regression model determination coefficient R 2 = 0.97, AdjR 2 = 0.93, which indicated that the model could better describe the experimental results.

[0093] Table 5 Regression model variance analysis

[0094]

[0095] The optimization function of Design-Expert 8.0 software was used to set the effect of auxiliary material to main material ratio, flavoring agent addition, and ethanol concentration on the change of dependent variable (comprehensive score), and the response surface graph was obtained, as Figure 6The optimal formula of the product was obtained by verifying the model predicted formula of the oyster peptide lactation granules, and the optimal formula of the product was as follows: auxiliary material: main material = 1.77:1, flavoring agent 15%, and ethanol concentration 79%. The amount of each component was converted into a mass percentage: oyster peptide 20%, astragalus polysaccharide 8.5%, soy isoflavone 1.7%, ginger powder 2.1%, papaya powder 2.1%, and brown sugar 10.7%; the auxiliary materials included mannitol 36.2% and lactose 18.1%, and the alcohol concentration was 79%.

[0096] Example 4: Activity verification of oyster peptide lactation granules

[0097] In this example, SPF KM mice were treated according to the method in Example 1, and 32 female mice with a difference of no more than 24 h in the time of giving birth were taken as experimental objects and randomly divided into a blank group, a model group, a positive control group, and an oyster peptide lactation granule group (prepared according to the optimal formula in Example 3), with 8 mice in each group. Bromocriptine mesylate was used for modeling, and blood supplementing and milk producing granules were used as a positive control.

[0098] The blank group was given distilled water by gavage, 5 mL / kg, twice a day;

[0099] The model group was given a dose of 8 mg / kg of bromocriptine mesylate solution by gavage at 9 o'clock in the morning and distilled water 5 mL / kg at 3 o'clock in the afternoon once a day.

[0100] The positive control group was given a dose of 8 mg / kg of bromocriptine mesylate solution by gavage at 9 o'clock in the morning and blood supplementing and milk producing granules 4272 mg / kg at 3 o'clock in the afternoon once a day.

[0101] The product group was given a dose of 8 mg / kg of bromocriptine mesylate solution by gavage at 9 o'clock in the morning and oyster peptide lactation granules 2000 mg / kg at 3 o'clock in the afternoon once a day.

[0102] The hourly milk production of the female mice and the weight loss of the female mice were recorded every day, and the female mice were sacrificed after the 10th day to collect blood and mammary gland tissue. The PRL and PRLR levels in the serum and mammary gland tissue of the female mice were determined.

[0103] The statistical results of the hourly milk production of the female mice are shown in Table 6. Compared with the blank group, the milk production of the female mice in the model group began to decrease significantly on the 4th day of administration (P<0.05), indicating that the bromocriptine-induced postpartum hypogalactia mouse model was successfully established. P <0.05). During the experimental period, the milk production of the female mice in each group decreased to different extents, and the decrease in the positive control group and the product group was smaller than that in the model group. P <0.05). During the experimental period, the milk production of the female mice in each group decreased to different extents, and the decrease in the positive control group and the product group was smaller than that in the model group.

[0104] Table 6. Milk production per hour by female mice

[0105]

[0106] Note: Comparison with model group* p <0.05 indicates a significant difference. p <0.01, the difference is highly significant; compared with the control group # p <0.05 indicates a significant difference. p <0.01 indicates a highly significant difference.

[0107] The amount of weight loss in the female mouse is as follows Figure 7 As shown, compared with the blank group, the body weight of the mother mice in the model group was significantly reduced. The body weight of the mother mice in the positive control group and the product group was less than that of the mother mice in the model group, and the differences were statistically significant. P <0.05). By Figure 8 It can be seen that the mammary gland organ index of the model group female mice was significantly lower than that of the control group. P <0.05); while the positive control group and the product group showed a significant recovery trend compared to the model group, indicating that oral administration of oyster peptide lactation-promoting granules is beneficial for the recovery of mammary glands in lactation-deficient mice.

[0108] Serum and breast tissue PRL and PRLR level measurement results are as follows Figure 9 As shown, compared with the blank group, the serum and mammary tissue levels of maternal mice in the model group were significantly reduced ( P <0.05); Compared with the model group, the serum and breast tissue PRL and PRLR levels in the product group were significantly increased ( P <0.05), serum PRL and PRLR increased by 19.84% and 19.79% respectively, and breast tissue PRL and PRLR increased by 25.70% and 13.61% respectively, indicating that oral administration of oyster peptide lactation-promoting granules can increase the level of lactation-related hormone PRL and increase PRLR content in serum and breast tissue.

[0109] In summary, oral administration of oyster peptide lactation-promoting granules can significantly increase milk production in lactating female mice, reduce weight loss, and significantly increase the mammary organ index. Furthermore, oral administration of oyster peptide lactation-promoting granules significantly increases the levels of PRL and PRLR in the serum and mammary tissue of female mice, leading to an increase in the number and enlargement of mammary alveoli. These results indicate that oyster peptide lactation-promoting granules can improve postpartum hypogalactia, promote mammary gland development, increase lactation-related hormones, and promote lactation.

[0110] The above embodiments are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above embodiments, and any changes, modifications, substitutions, combinations, simplifications, etc. made without departing from the spirit and principles of the present application should be equivalent replacement manners and should be included in the protection scope of the present application.

Claims

1. Use of a composition having a lactogenic effect for the manufacture of a medicament for the treatment of lactation failure, characterized in that, The composition is composed of oyster peptide, astragalus polysaccharide and soybean isoflavone; the mass ratio of the oyster peptide, astragalus polysaccharide and soybean isoflavone is 10-12:1-5:0.5-2.

2. A particle granule of oyster peptide with lactation-promoting effect, characterized in that, It is made of the following components: Main ingredients: oyster peptide, astragalus polysaccharide and soybean isoflavone; Auxiliary ingredients: mannitol and lactose; Flavoring agents: ginger powder, papaya powder and brown sugar; The mass ratio of oyster peptide, astragalus polysaccharide and soybean isoflavone in the main ingredients is 12:5:1; The mass ratio of the auxiliary ingredients to the main ingredients is 1:1-2, and the mass ratio of mannitol to lactose in the auxiliary ingredients is 1-2:1; The mass ratio of brown sugar, papaya powder and ginger powder in the flavoring agents is 4-6:1-1.5:1-1.5, and the amount is 15-25%.

3. The method for preparing the granules of oyster peptide of claim 2, characterized in that, Mix and stir the components of the oyster peptide granule of claim 2 until they are uniform, sieve them, make them into soft material with edible alcohol, sieve them again, dry them at 55-60℃ for 2-5h, sieve them again, and then finish the oyster peptide granule.

4. The method of claim 3, wherein, Edible alcohol with a concentration of 75-95% and a content of 10%-12% is used.

Images