Use of perillyl alcohol in the preparation of a medicament for the treatment of postpartum lack of lactation

Abstract

The application provides a use of perillaldehyde in preparation of a medicine for treating postpartum lack of lactation, and animal experiments show that perillaldehyde can effectively increase the lactation of postpartum lack of lactation female mice, significantly increase the litter weight growth rate of postpartum lack of lactation female mice, and improve the pathological state of mammary gland tissue of postpartum lack of lactation female mice. In addition, perillaldehyde has good safety and almost no side effects on the body. Therefore, the perillaldehyde described in the application can be used as an active ingredient and applied to preparation of a medicine for treating postpartum lack of lactation, thereby developing a new use of perillaldehyde and providing a new selection for preparation of a medicine for promoting lactation secretion and treating postpartum lack of lactation.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of biological medicine, and particularly relates to the use of perillaldehyde in the preparation of a drug for treating postpartum lack of lactation. BACKGROUND

[0002] Postpartum lack of lactation refers to a clinical common disease that a woman has less or no secretion of milk during the lactation period, so that the infant is insufficiently fed. Breastfeeding not only protects the mother from breast cancer, ovarian cancer and type 2 diabetes, but is also crucial to the health of the infant. Breast milk is an important source of nutrition for infants and young children, and the bioactive molecules in breast milk can improve the cognitive development of infants, reduce the incidence of infection and the risk of neonatal death. The World Health Organization and the United Nations Children's Fund strongly call for breastfeeding and recommend that infants under 6 months old be exclusively breastfed. However, milk secretion is often affected by factors such as diet, environment and mood, and lactation disorders are a common clinical problem for women during lactation. Therefore, it is important to find a drug that can be used to prepare a drug for enhancing milk secretion.

[0003] Perilla frutescens (L.) Britt. is an annual herbaceous plant of the Labiatae family, and the whole plant can be used as medicine. It is mainly distributed in Anhui, Hubei, Sichuan and other regions. At present, the Perilla frutescens is divided into four varieties, namely Perilla frutescens var. frutescens, Perilla frutescens var. arguta (original variety), Perilla frutescens var. crispa (also known as chicken comb Perilla frutescens) and wild Perilla frutescens var. purpurascens. Perilla has a long history of medicinal use, and the earliest record of its use in medicine is in Shanghan Zabing. It has the effects of relieving the exterior and dispelling cold, promoting qi and regulating the stomach, and can be used for colds, cough and vomiting, pregnancy vomiting, fish and crab poisoning, etc. It is a plant that can be used as medicine and food. The main chemical components of Perilla are small molecular monoterpenes, such as perillaldehyde, perilene, perilene, perillaketone, etc. Perillaldehyde, as the main natural monoterpene of Perilla, has various pharmacological activities, including anti-inflammatory, antifungal, antioxidant, neuroprotective and other pharmacological effects. The State Food and Drug Administration has clearly stipulated that perillaldehyde can be used as a natural food additive in food, and has good safety.

[0004] Although Perilla has a long history of medicinal use, through the review of relevant literature at home and abroad, it is found that there is a lack of research on the use of perillaldehyde for treating postpartum lack of lactation. Therefore, the study of the effect of perillaldehyde in improving lactation disorders has certain significance for the preparation of drugs for treating postpartum lack of lactation. SUMMARY

[0005] To solve the above technical problems in the prior art, the present application provides a new use of perillaldehyde, in particular, an application of perillaldehyde in preparation of a medicine for treating postpartum lack of lactation. Although perilla has a long history of medicinal use, there is no report on the effect of perillaldehyde, the main active ingredient of perilla, on treating postpartum lack of lactation at home and abroad.

[0006] The technical scheme of the present application is as follows:

[0007] The first object of the present application is to provide an application of perillaldehyde in preparation of a medicine for treating postpartum lack of lactation.

[0008] The second object of the present application is to provide an application of a pharmaceutical composition comprising perillaldehyde in preparation of a medicine for treating postpartum lack of lactation.

[0009] In the treatment of postpartum lack of lactation, perillaldehyde is used as an active ingredient, and various different dosage forms of the medicine which can be used in clinic are prepared by using a conventional preparation process, alone or in combination with other medicines.

[0010] Further, the dosage form of the medicine is a nasal drop, a powder, a pill, a capsule, a tablet, an injection, a powder, a granule, or an aerosol.

[0011] Further, the medicine further comprises a pharmaceutically acceptable excipient.

[0012] The active ingredient perillaldehyde of the medicine for treating postpartum lack of lactation has a significant effect of increasing the lactation amount of postpartum lack of lactation mother mice per hour, has a significant effect of increasing the litter weight growth rate of postpartum lack of lactation mother mice, can improve the pathological state of the mammary gland tissue of postpartum lack of lactation mother mice, and can be used for preparing a medicine for treating postpartum lack of lactation.

[0013] The present application has the following beneficial effects:

[0014] The perillaldehyde of the present application can effectively increase the lactation amount of postpartum lack of lactation mother mice, and in animal experiments, it is confirmed that the perillaldehyde can significantly increase the litter weight growth rate of postpartum lack of lactation mother mice and improve the pathological state of the mammary gland tissue of postpartum lack of lactation mother mice. In addition, the perillaldehyde has good safety and almost no side effects on the body. Therefore, the perillaldehyde of the present application can be used as an active ingredient and applied to the preparation of a medicine for treating postpartum lack of lactation, which opens up a new use of perillaldehyde and provides a new choice for preparing a medicine for promoting lactation secretion and treating postpartum lack of lactation. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 Effect of perillaldehyde on postpartum lactation amount of postpartum lack of lactation mice;

[0016] Figure 2 Effect of perillaldehyde on litter weight growth rate of postpartum lack of lactation mother mice;

[0017] Figure 3 Pathological observation results of breast tissue in each group. Detailed Implementation

[0018] The present invention will be further explained below with reference to the embodiments, but the embodiments do not limit the present invention in any way.

[0019] Example 1: Determination of milk production per hour in female mice after giving birth

[0020] S1, Experimental Materials

[0021] (1) Experimental animals: 8-week-old female and male ICR rats;

[0022] (2) Modeling reagent: Bromocriptine mesylate tablets

[0023] (3) Test drug: perillaldehyde

[0024] S2. Animal experimental methods

[0025] (1) Grouping of experimental animals

[0026] Mice were housed together at a female-to-male ratio of 2:1. Female mice exhibiting vaginal plugs were selected and housed individually. After giving birth, 32 female mice with a short time interval (approximately 24 hours) were selected as experimental subjects. These 32 selected female mice were randomly divided into 4 groups of 8 mice each: a blank control group, a hypogalactia model group (bromocriptine), a low-dose perillaldehyde group (30 mg / kg), and a high-dose perillaldehyde group (90 mg / kg). First, perillaldehyde was dissolved in 0.5% CMC-Na. Starting from the second day after birth (PD1), the first group of mother mice served as a blank control group and were administered physiological saline and 0.5% CMC-Na by gavage. The second group of mother mice served as a hypogalactia model group and were administered bromocriptine solution (1.6 mg / ml) and 0.5% CMC-Na by gavage. The third and fourth groups served as the low-dose perillaldehyde group and the high-dose perillaldehyde group, respectively, and were simultaneously given bromocriptine solution and perillaldehyde solution (30 mg / kg and 90 mg / kg), twice a day for 13 days.

[0027] (2) Determination of milk production in experimental female rats

[0028] Changes in maternal milk production were determined by weighing the litter of pups. Records were taken every other day for 7 days.

[0029] The effect of perillaldehyde on milk production in postpartum lactation-deficient mice is as follows: Figure 1As shown, the hourly milk secretion of the postpartum lack of milk model group was significantly lower than that of the blank control group from postpartum day 4 (PD3) (P<0.05), indicating that the postpartum lack of milk mouse model was successfully established by bromocriptine. In addition, the hourly milk secretion of the perilla aldehyde high-dose group was significantly higher than that of the model lack of milk group from postpartum day 6 (PD5) (P<0.05); the hourly milk secretion of the perilla aldehyde low-dose group was significantly higher than that of the model lack of milk group from postpartum day 8 (PD7) (P<0.05). At the same time, there was no significant difference in the hourly milk secretion of the perilla aldehyde treatment groups compared with the blank control group.

[0030] Measurement of the growth rate of the litter weight of the offspring in Example 2

[0031] S1, Experimental materials

[0032] (1) Experimental animals: 8-week-old ICR female and male mice;

[0033] (2) Model reagent: bromocriptine mesylate tablets

[0034] (3) Test drug: perilla aldehyde

[0035] S2, Animal experiment method

[0036] (1) Experimental animal grouping

[0037] The mice were bred in the same cage at a ratio of 2:1, and the female mice with vaginal plugs were selected and bred in single cages. After the female mice gave birth to offspring, 32 female mice with a short time difference (about 24 h) were selected as experimental objects, and the 32 female mice were randomly divided into 4 groups of 8 each, namely, a blank control group, a lack of milk model group (bromocriptine), a perilla aldehyde low-dose group (30 mg / kg), and a perilla aldehyde high-dose group (90 mg / kg). The perilla aldehyde was dissolved in 0.5% CMC-Na, and on the second day after birth (recorded as PD1), the first group of female mice were given normal saline and 0.5% CMC-Na by gavage as the blank control group, the second group of female mice were given bromocriptine solution (1.6 mg / ml) and 0.5% CMC-Na by gavage as the lack of milk model group, and the third and fourth groups were given bromocriptine solution and perilla aldehyde solution (30 mg / kg, 90 mg / kg) by gavage as the perilla aldehyde low-dose group and the perilla aldehyde high-dose group, twice a day, for 13 days.

[0038] (2) Measurement of the growth rate of the litter weight of the offspring of the experimental animal female mice

[0039] The change in the growth rate of the litter weight of the offspring was determined by weighing the body weight of the offspring on postpartum day 2 (PD1) and postpartum day 14 (PD13).

[0040] The results of the effect of perilla aldehyde on the growth rate of the litter weight of the offspring of postpartum lack of milk female mice are as follows Figure 2As shown in the figure, compared with the blank control group, the litter weight growth rate of the milk deficiency model group was significantly reduced, and there was a significant difference (P<0.001); while the low-dose and high-dose perillaldehyde treatment groups could significantly increase the litter weight growth rate of the postpartum milk deficiency mother mice, and there was a significant difference (P<0.05); at the same time, the litter weight growth rate of the perillaldehyde treatment group had no significant difference compared with the blank control group.

[0041] Example 3 Histopathological observation of the mammary gland tissue of the mother mouse

[0042] S1, experimental materials

[0043] (1) Experimental animals: 8-week-old ICR female and male mice;

[0044] (2) Model reagent: bromocriptine mesylate tablets

[0045] (3) Test drug: perillaldehyde

[0046] S2, animal experiment method

[0047] (1) Experimental animal grouping

[0048] The mice were bred in the same cage according to the ratio of 2:1, and the mother mice with vaginal plugs were selected and bred in single cages. After the mother mice gave birth to the pups, 32 mother mice with short time difference (about 24h) were selected as experimental objects, and the 32 selected mother mice were randomly divided into 4 groups, each group with 8 mother mice, which were blank control group, milk deficiency model group (bromocriptine), low-dose perillaldehyde group (30mg / kg) and high-dose perillaldehyde group (90mg / kg). First, the perillaldehyde was dissolved in 0.5% CMC-Na, and on the second day after birth (recorded as PD1), the first group of mother mice were given normal saline and 0.5% CMC-Na as blank control group, the second group of mother mice were given bromocriptine solution (1.6mg / ml) and 0.5% CMC-Na as milk deficiency model group, and the third and fourth groups were given bromocriptine solution and perillaldehyde solution (30mg / kg, 90mg / kg) as low-dose perillaldehyde group and high-dose perillaldehyde group, twice a day, for 13 days.

[0049] (2) Histopathological observation of the mammary gland tissue of the experimental animal mother mouse

[0050] After the mother mouse was executed by cervical dislocation, the mammary glands at the same position were fixed in 4% paraformaldehyde, paraffin-embedded, sectioned, HE stained, and the histomorphology of the mammary glands was observed under an optical microscope.

[0051] The results of the histopathological observation of the mammary glands in each group are as follows Figure 3As shown, compared with the blank control group, the mammary connective tissue of the bromocriptine lactation model group mice was obviously increased, the alveoli were smaller, and the mammary lobules were less; compared with the bromocriptine lactation model group, the number of mammary alveoli and mammary lobules of the low-dose and high-dose perilla aldehyde treatment groups were obviously increased.

[0052] The above merely describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. Application of perillaldehyde as the sole active ingredient in the preparation of drugs for treating postpartum hypogalactia.

2. The application according to claim 1, characterized in that, The dosage forms of the drug are powder, pill, capsule, tablet, injection, powder, and granule.

3. The application according to claim 1, characterized in that, The drug also includes pharmaceutically acceptable excipients.

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