Application of traditional Chinese medicine composition for regulating menstruation and promoting pregnancy in preparation of medicine for promoting early embryo development of in-vitro fertilization-embryo transplantation

Abstract

The invention relates to a traditional Chinese medicine composition, in particular to application of a menstruation regulating and pregnancy promoting pill traditional Chinese medicine composition in preparation of a medicine for promoting early embryo development of in-vitro fertilization-embryo transplantation. According to the application of the menstruation-regulating and pregnancy-promoting traditional Chinese medicine composition in preparation of the medicine for promoting early embryo development of in-vitro fertilization-embryo transplantation, the research finds that after administration intervention of the menstruation-regulating and pregnancy-promoting medicine composition, the total ovulation number and fertilization number of mice can be increased, the development number and development condition of fertilized eggs are promoted, and the blastocyst quality is improved; the research on the effect of the menstruation regulating and pregnancy promoting pill on the in-vitro fertilization is carried out, the effect and the effect characteristics of the medicine on the mouse ovulation function and the fertilized egg development quality are defined, the new application of the medicine is expanded, and a new effective medicine and means are provided for the assisted reproduction technology, so that the technical support is provided for the reasonable application of the medicine.

Description

Technical Field

[0001] The invention relates to a Chinese medicine composition, in particular to use of a Chinese medicine composition of a menstruation regulating and pregnancy promoting pill in preparing a medicine for promoting early embryo development in in vitro fertilization-embryo transplantation. Background Art

[0002] Due to environmental pollution, work pressure, and lifestyle, the incidence of infertility is increasing year by year worldwide. According to WHO data, there are 48 million couples and 186 million people suffering from infertility worldwide. Traditional treatments for infertility are limited, including Chinese and Western medicine, surgical treatment, psychological counseling, etc., but these treatments have disadvantages such as long cycles and poor results. In recent years, assisted reproductive technology has developed rapidly and has become the mainstream technology for treating infertility. Among infertile patients, at least 20% of couples need assisted reproductive technology to achieve fertility. Assisted reproductive technology refers to an invasive operation that uses gametes, embryos or genetic materials to perform a series of in vitro and in vivo system operations to obtain new life, mainly including artificial insemination and in vitro fertilization-embryo transfer (IVF-ET) and its related derivative technologies. IVF-ET technology is widely used in the treatment of infertility caused by ovarian failure, endometriosis, and polycystic ovary syndrome, but data show that the early miscarriage rate of patients receiving IVF-ET treatment is 16.16%, mainly due to embryo quality, endometrial receptivity, and transplantation technology. Egg quality is affected by age, living environment, and mental stress, which directly affects early embryo development, the establishment and maintenance of pregnancy, and fetal development. In IVF-ET, egg quality and the quality of early embryos formed become the decisive factors for success. How to improve the success rate of assisted reproductive technology has attracted widespread attention from scientific researchers, and exploring ways to improve egg quality and pre-transplant embryo quality has become one of the entry points. Summary of the invention

[0003] Therefore, the technical problem to be solved by the present invention is to provide a use of a Chinese medicine composition of a menstruation regulating and pregnancy promoting pill in the preparation of a drug for promoting early embryo development in in vitro fertilization-embryo transfer.

[0004] To this end, the present invention provides the following technical solutions:

[0005] A use of a menstruation regulating and pregnancy promoting Chinese medicinal composition in the preparation of a medicine for promoting early embryo development in in vitro fertilization-embryo transplantation.

[0006] Optionally, the promoting early embryo development in vitro fertilization-embryo transfer includes increasing the number of ovulations, increasing the number of fertilized eggs, increasing the number of blastocysts and / or improving the quality of early embryos.

[0007] Optionally, improving the quality of early embryos includes improving blastocyst formation rate and / or tissue structure.

[0008] Optionally, the raw materials of the Chinese medicine composition for regulating menstruation and promoting pregnancy include: pilose antler, epimedium, curculigo, radix dipsaci, parasitic plant, dodder seed, wolfberry, raspberry, yam, lotus seed, poria, astragalus, white peony root, spiny jujube seed, Uncaria rhynchophylla, salvia miltiorrhiza, red peony root and millettia reticulata

[0009] Optionally, the antler is a depilated antler;

[0010] And / or, the epimedium is roasted epimedium;

[0011] And / or, the lotus seeds are cored lotus seeds;

[0012] And / or, the Chinese jujube seeds are stir-fried Chinese jujube seeds.

[0013] Optionally, the Chinese medicine composition for regulating menstruation and promoting pregnancy includes the following raw materials in parts by weight: 5-15 parts of pilose antler, 10-30 parts of epimedium, 10-40 parts of curculigo, 10-30 parts of dipsaccharum, 10-30 parts of villous plant, 15-50 parts of dodder seeds, 10-30 parts of wolfberry, 10-30 parts of raspberry, 30-60 parts of yam, 10-30 parts of lotus seeds, 15-50 parts of poria, 10-30 parts of astragalus, 15-50 parts of white peony root, 10-30 parts of spiny jujube seed, 10-30 parts of Uncaria rhynchophylla, 15-50 parts of salvia miltiorrhiza, 15-50 parts of red peony root and 30-60 parts of Millettia reticulata.

[0014] Optionally, the Chinese medicine composition for regulating menstruation and promoting pregnancy includes the following raw materials in parts by weight: 5 parts of pilose antler, 10 parts of roasted epimedium, 10 parts of curculigo, 10 parts of dipsaccharum, 10 parts of villous plant, 15 parts of dodder seeds, 10 parts of wolfberry, 10 parts of raspberry, 30 parts of yam, 10 parts of lotus seeds, 15 parts of poria, 10 parts of astragalus, 15 parts of white peony root, 10 parts of stir-fried spiny jujube seeds, 10 parts of Uncaria rhynchophylla, 15 parts of salvia miltiorrhiza, 15 parts of red peony root, and 30 parts of Millettia reticulata.

[0015] Optionally, the Chinese herbal composition for regulating menstruation and promoting pregnancy is prepared into a pharmaceutically acceptable preparation by weighing raw materials according to a formula, adding or not adding auxiliary materials.

[0016] Optionally, the formulation includes a liquid form, a semi-solid form or a solid form.

[0017] Optionally, the dosage form of the preparation includes tablets, pills, granules, capsules, injections, oral liquids, powders, suspensions, syrups, drops, lyophilized products or decoctions.

[0018] In traditional Chinese medicine theory, infertility is called "complete infertility", "childlessness", "intermittent", etc., and according to the patient's medical history and the clinical manifestations and signs of the four diagnoses, dialectical classification is carried out, namely, kidney qi deficiency syndrome, kidney yang deficiency syndrome, kidney yin deficiency syndrome, kidney deficiency and blood stasis syndrome, liver depression syndrome, phlegm dampness syndrome, blood stasis syndrome and other syndromes. Male sperm is strong, female menstruation is regulated: "The coming of life is called sperm, and the fighting of two sperms is called spirit", which is the mechanism of female conception. "Nu Ke Zheng Zong" says: "Male sperm is strong and female menstruation is regulated, which is the way to have children." Male sperm is strong means that male semen and sexual function are normal; female menstruation is normal, and female period, volume, color, quality, and periodic ovulation are normal. "Fu Ke Bu Jie - Menstruation Regulation" emphasizes: "Most women's diseases are caused by irregular menstruation. After menstruation is regulated, they can conceive and eliminate diseases, so regulating menstruation is the first priority." The "Zhengzhi Zhunsheng·Gynecology·Prenatal Gate" points out: "Every time a woman has her menstruation, there must be a day of misty signs... This is the sign... If it is applied smoothly, the fetus will be formed." It can be seen from this that the mechanism of conception lies in the fullness of the kidney qi of men and women, the maturity of the heavenly essence, the fullness of the Ren meridian, the regulation of the menstruation, and the timely harmony, which will lead to the fetus. "The two spirits fight and combine to form" is the beginning of pregnancy, and "ten months of pregnancy and one day of delivery" is the end of pregnancy. "The Heart of Pregnancy and Childbirth" says: "When a woman is pregnant, her blood stays and her qi gathers, and the uterus is full." The uterus is connected to the kidney, and the Chong and Ren meridians both originate in the uterus. The fetus lives in the mother's body, relying entirely on the mother's kidney to connect it, the qi to carry it, the blood to nourish it, and the Chong and Ren meridians to consolidate it. If the mother's kidney qi is strong, the qi and blood are full, and the Chong and Ren meridians are smooth, the fetus will be solid and the mother will be safe. Therefore, kidney deficiency, deficiency of both qi and blood, qi stagnation and blood stasis after pregnancy are the causes of the disease, and damage to Chong and Ren meridians and instability of the fetal origin are the pathogenesis. The treatment method is based on the principle of "pre-cultivation of damage, combination of prevention and treatment". In addition, "Suwen Four Qi Tiao Shen Da Lun" says "Therefore, the sage does not treat the disease, but treats the disease before it occurs; does not treat the disorder, but treats the disorder before it occurs. This is what it means. If the disease is already formed and then the medicine is taken, and the disorder is already formed and then treated, it is like digging a well when thirsty, and casting an awl when fighting. Isn't it too late?" Therefore, the best doctor treats the disease before it occurs, and must prevent it before it happens. Therefore, we should pay attention to conditioning before pregnancy, so that "positive qi is stored inside, and evil cannot interfere", so as to fill the state of pregnancy, protect the fetus after pregnancy, and achieve "yin and yang coordination, form and spirit together" to help the fetus grow steadily and achieve both pregnancy and delivery.

[0019] The pills for regulating menstruation and promoting pregnancy are composed of velvet antler (dehaired), epimedium (roasted), curculigo, radix scutellariae, mistletoe, dodder seed, wolfberry fruit, raspberry, yam, lotus seed (core removed), tuckahoe, astragalus, white peony root, spiny jujube seed (fried), Uncaria rhynchophylla, salvia miltiorrhiza, red peony root, and millettia spatholobi. Velvet antler and radix scutellariae strengthen yang and warm the kidney; mistletoe nourishes the liver and kidney, epimedium and dodder seed regulate the Chong and Ren meridians, nourish yin and tonify the kidney; lotus seed has the effect of tonifying the middle meridian and strengthening the spleen, and astragalus has the effect of tonifying qi and raising yang, and strengthening qi and strengthening the exterior; spiny jujube seed nourishes yin and blood, white peony root and salvia miltiorrhiza nourish blood and regulate menstruation, Chinese yam nourishes the kidney and warms the essence, tuckahoe strengthens the spleen and eliminates dampness, and millettia spatholobi promotes blood circulation and removes blood stasis. The combination of these medicines can play the effect of regulating the Chong and Ren meridians, strengthening the spleen and tonifying the kidney, nourishing blood, regulating menstruation and promoting pregnancy. The present invention evaluates the effect of the menstruation regulating and pregnancy promoting pill drug combination on the ovulation function and egg quality after intervention on the mother based on in vitro fertilization technology, and simultaneously monitors the development quality and success rate of the fertilized egg gradually developing to the blastocyst stage, explores the effect of the menstruation regulating and pregnancy promoting pill drug combination on the quality of early embryos before transplantation in assisted reproductive technology, and provides new ideas for improving the success rate of assisted reproduction and improving infertility. The study found that the menstruation regulating and pregnancy promoting drug combination can increase the total number of ovulations and fertilizations in mice, promote the number and development status of fertilized eggs, and improve the quality of blastocysts after administration intervention. Through the study on the effect of the menstruation regulating and pregnancy promoting pill on in vitro fertilization, the effect and characteristics of the drug on the ovulation function and development quality of fertilized eggs in mice are clarified, the new use of the drug is expanded, and new effective drugs and means are provided for assisted reproductive technology, thereby providing technical support for the rational application of drugs.

[0020] The technical solution of the present invention has the following advantages:

[0021] 1. Use of a menstruation regulating and pregnancy promoting Chinese medicine composition in the preparation of a drug for promoting early embryonic development in vitro fertilization-embryo transfer. The present invention has found that the drug composition for regulating menstruation and promoting pregnancy can increase the total number of ovulations and fertilizations of mice, promote the number and development status of fertilized eggs, and improve the quality of blastocysts after administration intervention. After conducting a study on the effect of the menstruation regulating and pregnancy promoting pills on in vitro fertilization, the effect and characteristics of the drug on the ovulation function of mice and the quality of fertilized egg development were clarified, the new use of the drug was expanded, and new effective drugs and means were provided for assisted reproductive technology, thereby providing technical support for the rational application of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 These are the microscopic examination results of embryo morphology at different stages of embryonic development in the experimental examples of the present invention. DETAILED DESCRIPTION

[0024] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0025] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0026] The 2-cell stage, 4-cell stage, 8-cell stage and blastocyst stage embryos involved in the following embodiments are the process of embryonic development. For example, the 2-cell stage refers to the early embryonic development stage after fertilization, which is a term for the fertilized egg development stage. See [Yao C, Zhang W, Shuai L. The first cell fate decision in pre-implantation mouse embryos. Cell Regen. 2019 Nov 20; 8(2): 51-57. doi: 10.1016 / j.cr.2019.10.001. PMID: 31844518; PMCID: PMC6895705.].

[0027] Example 1

[0028] 1. Purpose of the experiment

[0029] To explore the effects of Tiaojing Cuyun Pills on ovulation function, egg quality and early embryonic development based on in vitro fertilization, and to evaluate the pharmacodynamics of Tiaojing Cuyun Pills.

[0030] 2. Experimental design

[0031] The in vitro development of the embryo includes fertilization, cleavage and blastocyst formation, which is a dynamic and continuous process. Therefore, by administering "Tiaojing Cuyu Wan" to evaluate the ovulation function of female mice and to detect the quality and developmental potential of the embryo in vitro, the efficacy of the test substance can be evaluated to a certain extent.

[0032] In order to evaluate the effect of Tiaojing Cuyun Pill on ovulation function, egg quality and late embryo development, this experiment used in vitro fertilization to establish a pharmacodynamic evaluation system, using C57BL / 6J mice as the research subjects. After multiple drug interventions, the mice in the drug group were screened for estrus to collect eggs, and co-cultured with donor sperm for a certain period of time, and finally collected fertilized eggs for in vitro embryo culture. During the experiment, indicators such as ovulation number, fertilization number, embryo development, and embryo development morphology were detected.

[0033] This method uses in vitro fertilization technology to carry out a study on the efficacy of Tiaojing Cuyun Pill on the ovulation function of female mice and the in vitro development of embryos. The results show that after the mice were given different doses of Tiaojing Cuyun Pill intervention, the number of embryos produced was more than that of the control group, the embryo quality was better, and the in vitro cultured embryos developed better.

[0034] 3 Experimental animals and drug administration information

[0035] 3.1 Animal information

[0036] C57BL / 6J mice were obtained from the Institute of Laboratory Animal Resources, China Food and Drug Inspection Institute. They were 3 to 4 weeks old and weighed approximately 14 to 18 g. Number: 45, female. Laboratory Animal Production License Number: SCXK (Beijing) 2022-0002, Laboratory Animal Use License Number: SYXK (Beijing) 2022-0014. The animal grouping and experimental environment adaptation period was 5 to 7 days. The mice were fed SPF-grade mouse pellet feed and had free access to sterilized tap water. The room temperature was 20 to 26°C, the relative humidity was 40% to 70%, and the lighting was 12 hours light / 12 hours dark. This experiment was conducted under the supervision of the Laboratory Animal Welfare Ethics Review Committee of the China Food and Drug Inspection Institute, and the Welfare Ethics Review Number: China Inspection Animal (Fu) No. 2023 (B) 007.

[0037] 3.2 Dosage regimen and dosage setting

[0038] After passing the quarantine, the mice were divided into three groups, namely the high-dose group, low-dose group and control group of Tiaojing Cuyun Pills, with 15 mice in each group. Tiaojing Cuyun Pills (Tong Ren Tang Pharmaceutical Factory, Beijing Tong Ren Tang Co., Ltd., 22035305) were mixed with pure water to form a suspension for administration. The high and low doses were 10.275g / kg (mouse body weight) and 2.055g / kg (mouse body weight), respectively; the control group was given pure water. The animals were given drugs starting 3 weeks before the in vitro fertilization experiment, and the drugs were administered by gavage daily, 5 days a week, and the administration cycle was 3 weeks.

[0039] Table 1 Experimental groups

[0040]

[0041]

[0042] 4. Test methods and test indicators

[0043] 4.1 Oocyte collection and fertilization

[0044] In order to maintain the parallelism of the experiment, estrus mice screening was required before egg collection. After 3 weeks of drug administration, the mice were tested for estrus, and 3 mice that entered estrus synchronously were randomly selected from each group to collect eggs, and the number of ovulation and fertilization of 3 mice in each group was counted. After disinfection and dissection of 3 mice, the bilateral oviducts of female mice were removed, and the enlarged part of the oviduct ampulla was punctured with a syringe needle, and the oocytes were taken out and placed in the pre-equilibrated HTF culture medium (purchased from ARK resource, batch number 21022). Male mice were killed by cervical dislocation, and the bilateral epididymis was taken. A small incision was made with Venus scissors to release sperm into the pre-equilibrated PM sperm capacitation solution (purchased from Kyudo, batch number CK2201P) and cultured at 37°C for one hour. The sperm at the edge of the PM culture solution (purchased from ARKresource, batch number 20022) was aspirated and injected into the HTF culture medium containing oocytes, and the volume fraction was 5% CO. 2 After culturing in a 37°C incubator for 18 to 20 hours, the 2-cell stage after fertilization was observed and counted. After in vitro fertilization, the total number of ovulations and fertilized eggs, as well as the results of in vitro development experiments after fertilization of eggs were further calculated and compared.

[0045] 4.2 Statistical analysis of embryo numbers and development at different stages of embryonic development

[0046] From the fertilized embryos of the high-dose group, low-dose group and control group, 20 were randomly selected for in vitro embryo culture to observe the number and status of embryos at the 2-cell stage, 4-cell stage, 8-cell stage and blastocyst stage. The embryonic development at the four different stages of the 2-cell stage, 4-cell stage, 8-cell stage and blastocyst stage was observed under a microscope.

[0047] 5 Experimental results

[0048] 5.1 Effects of Tiaojing Cuyun Pills on Ovulation and Fertilization in Mice

[0049] The test results showed that the total number of ovulations and the number of fertilized eggs in the drug-treated group were higher than those in the control group, as shown in Table 2.

[0050] Table 2 Ovulation and fertilization of mice in each group

[0051] Grouping Total ovulation number Fertilization number Number of unfertilized High dose group 29 26 3 Low dose group 26 25 1 Control group 23 22 1

[0052] Note: 3 mice were included in each group.

[0053] 5.2 Effects of Tiaojing Cuyun Pills on Embryonic Development

[0054] Blastocyst is the highest stage of embryo culture in vitro and is also the stage when human embryos are implanted into the mother, so in vitro observation only stops at the blastocyst stage. As shown in the experimental results, the high-dose group had the largest number of blastocysts and the highest proportion, and the embryo development was better than other groups, indicating that the embryo quality was better. The results of embryo development in each group of mice are shown in Tables 3 and 4. The cleavage rate of 2-cell embryos of mice in the high, low, and control dose groups showed a decreasing trend; the blastocyst formation rate of mice in the high and low dose groups was higher than that in the control group, and there was a dose effect. The blastocyst is composed of the blastocyst cavity, inner cell mass, and trophoblast cell membrane. The blastocyst in the high-dose group was more mature, the inner cell mass had a large number of cells, and the structure was tightly arranged, while the inner cell mass in the control group had a small number of cells and a loosely arranged structure. Figure 1 .

[0055] Table 3 Statistics of embryonic development of mice in each group

[0056] Grouping 2 cells 4 cells 8 cells Blastocyst High dose group 20 20 20 13 Low dose group 20 18 17 12 Control group 20 17 16 11

[0057] Note: Compared with the control group, * means p < 0.05.

[0058] Table 4 Statistics of embryonic development percentage of mice in each group

[0059]

[0060]

[0061] Note: Compared with the control group, * means p < 0.05.

[0062] In summary, the administration of Tiaojing Cuyun Pills can increase the total number of ovulations and fertilizations in mice, promote the number and development of fertilized eggs, and improve the quality of blastocysts. The study of the effect of Tiaojing Cuyun Pills on in vitro fertilization has clarified the effects and characteristics of the drug on the ovulation function and development quality of fertilized eggs in mice, expanded the new uses of the drug, provided new effective drugs and means for assisted reproductive technology, and thus provided technical support for the rational use of drugs.

[0063] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. Use of a Chinese medicine composition for regulating menstruation and promoting pregnancy in the preparation of a drug for promoting early embryo development in in vitro fertilization-embryo transfer.

2. The use according to claim 1, characterized in that The promoting of early embryo development in vitro fertilization-embryo transfer includes increasing the number of ovulations, increasing the number of fertilized eggs, increasing the number of blastocysts and / or improving the quality of early embryos.

3. The use according to claim 2, characterized in that: Improving the quality of early embryos includes improving the blastocyst formation rate and / or tissue structure.

4. The use according to any one of claims 1 to 3, characterized in that: The raw materials of the Chinese medicine composition for regulating menstruation and promoting pregnancy include: pilose antler, epimedium, curculigo, dipsacus, mistletoe, dodder seed, wolfberry fruit, raspberry, yam, lotus seed, tuckahoe, astragalus, white peony root, spiny jujube seed, Uncaria rhynchophylla, salvia miltiorrhiza, red peony root and millettia reticulata.

5. The use according to any one of claim 4, characterized in that The velvet antler is a depilated velvet antler; And / or, the epimedium is roasted epimedium; And / or, the lotus seeds are cored lotus seeds; And / or, the Chinese jujube seeds are stir-fried Chinese jujube seeds.

6. The use according to any one of claims 4 or 5, characterized in that The Chinese medicine composition for regulating menstruation and promoting pregnancy comprises the following raw materials in parts by weight: 5-15 parts of pilose antler, 10-30 parts of epimedium, 10-40 parts of curculigo, 10-30 parts of dipsaccharum, 10-30 parts of villous plant, 15-50 parts of dodder seeds, 10-30 parts of wolfberry, 10-30 parts of raspberry, 30-60 parts of yam, 10-30 parts of lotus seeds, 15-50 parts of poria, 10-30 parts of astragalus, 15-50 parts of white peony root, 10-30 parts of spiny jujube seed, 10-30 parts of Uncaria rhynchophylla, 15-50 parts of salvia miltiorrhiza, 15-50 parts of red peony root and 30-60 parts of millettia reticulata.

7. The use according to claim 6, characterized in that The Chinese medicine composition for regulating menstruation and promoting pregnancy includes the following raw materials in parts by weight: 5 parts of pilose antler, 10 parts of roasted epimedium, 10 parts of curculigo, 10 parts of dipsaccharum, 10 parts of villous plant, 15 parts of dodder seeds, 10 parts of wolfberry, 10 parts of raspberry, 30 parts of yam, 10 parts of lotus seeds, 15 parts of poria, 10 parts of astragalus, 15 parts of white peony root, 10 parts of stir-fried spiny jujube seeds, 10 parts of Uncaria rhynchophylla, 15 parts of salvia miltiorrhiza, 15 parts of red peony root, and 30 parts of Millettia reticulata.

8. The use according to any one of claims 4 to 7, characterized in that: The Chinese medicine composition for regulating menstruation and promoting pregnancy is prepared into a pharmaceutically acceptable preparation by weighing raw materials according to a formula and adding or not adding auxiliary materials.

9. The use according to claim 8, characterized in that The formulation includes liquid form, semi-solid form or solid form.

10. The use according to claim 8 or 9, characterized in that The dosage form of the preparation includes tablets, pills, granules, capsules, injections, oral liquids, powders, suspensions, syrups, drops, lyophilized products or decoctions.

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