Oral liquid preparation containing eldecalciferol and preparation method thereof

Abstract

The invention discloses an oral liquid preparation containing eldecalciferol. The eldecalciferol oral liquid is prepared from the following components in parts by weight: 20 to 50 parts of eldecalciferol, 5 to 10 parts of polyoxyethylene hydrogenated castor oil, 10 to 15 parts of medium-chain fatty acid triglyceride, 10 to 15 parts of tocopherol, 10 to 15 parts of ethanol, 5 to 10 parts of purified water, 1 to 2 parts of citric acid, 1 to 2 parts of sorbitol, 0.5 to 1.0 part of a flavoring agent and 0.2 to 0.5 part of a bacteriostatic agent. The invention also provides a preparation method of the oral liquid preparation. The prepared oral liquid preparation containing eldecalciferol has an obvious treatment effect on osteoporosis symptoms caused by female menopause.

Description

Technical Field

[0001] The present invention relates to the field of oral liquid preparations. More specifically, the present invention relates to an oral liquid preparation containing eldecalcitol and a method for preparing the same. Background Art

[0002] Osteoporosis is a complex systemic bone disease caused by the combined action of multiple factors. Its core features are the dual decline of bone density and bone quality, while the bone microstructure is damaged, resulting in a significant increase in bone fragility, and thus the individual is in a high-risk state of being prone to fractures. Clinically, osteoporosis is mainly divided into two major categories: primary and secondary. Primary osteoporosis is further subdivided into postmenopausal osteoporosis (type I), senile osteoporosis (type II), and idiopathic osteoporosis.

[0003] Postmenopausal osteoporosis, as a common disease closely related to aging, mainly affects postmenopausal women. After menopause, the estrogen level in the body drops sharply, which disrupts the original balance of bone metabolism, leading to an accelerated loss of bone mass, and the bone tissue structure also changes accordingly. The trabeculae become thinner and fractured, the cortical bone becomes thinner, resulting in a significant reduction in the strength and toughness of the bone, a significant increase in bone fragility, and a substantial increase in the risk of fractures. Fractures not only cause severe pain to patients but also often lead to bone deformities and a series of serious complications, such as pulmonary infections and deep vein thrombosis. These problems seriously affect the physical health and quality of life of the elderly and may even shorten the patient's lifespan. In the entire market environment, research on postmenopausal osteoporosis in women is generally lacking. Although this group is large in scale and has urgent needs, the lag in related research has restricted the innovation and optimization of treatment methods. Conducting in-depth research on postmenopausal osteoporosis in women, especially targeted research on new drugs such as eldecalcitol, is of great significance for improving the health status and quality of life of this large group. Summary of the Invention

[0004] To achieve these and other advantages in accordance with the present invention, a preferred embodiment of the present invention provides an oral liquid preparation containing eldecalcitol, which is characterized by being prepared from the following components: eldecalcitol, polyoxyethylene hydrogenated castor oil, medium-chain triglyceride, tocopherol, ethanol, purified water, citric acid or its salt, sorbitol, flavoring agent, and bacteriostatic agent.

[0005] According to a preferred embodiment of the present invention, it is prepared from the following components in parts by weight:

[0006] 0.01 - 0.1 parts of eldecalcitol, 100 - 3000 parts of polyoxyethylene hydrogenated castor oil, 100 - 3000 parts of medium-chain triglycerides, 0.1 - 50 parts of tocopherol, 1000 - 3000 parts of ethanol, 5000 - 15000 parts of purified water, 50 - 200 parts of citric acid or its salt, 5000 - 10000 parts of sorbitol, 1 - 100 parts of flavoring agent, and 1 - 10 parts of bacteriostatic agent.

[0007] According to a preferred embodiment of the present invention, the bacteriostatic agent is any one or a combination of more than one of methylparaben, ethylparaben, propylparaben, butylparaben, and sodium benzoate.

[0008] According to a preferred embodiment of the present invention, the flavoring agent is any one or a combination of more than one of sucrose, sorbitol, xylitol, sucralose, and aspartame.

[0009] According to a preferred embodiment of the present invention, the dosage form of the oral liquid preparation containing eldecalcitol is selected from at least one of drops, syrup, oral emulsion, oral suspension, or oral solution.

[0010] On the other hand, the present application also provides a preparation method of the oral liquid preparation containing eldecalcitol, including the following steps:

[0011] Step S1: Take 1 / 2 of the above parts by weight of citric acid, sorbitol, flavoring agent, bacteriostatic agent, and purified water and mix them to obtain a first solution;

[0012] Step S2: Take eldecalcitol, polyoxyethylene hydrogenated castor oil, medium-chain triglycerides, tocopherol, and ethanol, mix them, and add the remaining purified water thereto to obtain a second solution;

[0013] Step S3: Mix the first solution and the second solution, adjust the pH value to 6 - 8 with a pH regulator, then filter and sterilize to obtain a sterile medicinal solution, and finally package it to obtain the target oral liquid preparation.

[0014] The present invention has at least the following beneficial effects: The oral liquid preparation containing eldecalcitol prepared by the present invention has an obvious therapeutic effect on the osteoporosis symptoms caused by female menopause.

[0015] Other advantages, objectives, and features of the present invention will be partially reflected by the following description, and partially will be understood by those skilled in the art through the research and practice of the present invention. Detailed Description of the Invention

[0016] The following further describes the present invention in detail with reference to examples, so that those skilled in the art can implement it according to the description in the specification.

[0017] The following description is used to disclose the present invention so that those skilled in the art can implement the present invention. The preferred embodiments in the following description are only examples, and those skilled in the art can think of other obvious deformations. The basic principles of the present invention defined in the following description can be applied to other implementation schemes, deformation schemes, improvement schemes, equivalent schemes, and other technical schemes that do not depart from the spirit and scope of the present invention.

[0018] Example 1

[0019] An oral liquid preparation containing eldecalcitol is provided, comprising the following components in parts by weight: 0.05 part of eldecalcitol, 500 parts of polyoxyethylene hydrogenated castor oil, 0.5 part of tocopherol, 1000 parts of ethanol, 15000 parts of purified water, 100 parts of citric acid, 10000 parts of sorbitol, 10 parts of flavoring agent, and 5 parts of bacteriostatic agent.

[0020] Example 2

[0021] 0.02 part of eldecalcitol, 400 parts of medium-chain triglycerides, 1 part of tocopherol, 3000 parts of ethanol, 10000 parts of purified water, 2 parts of citric acid, 8000 parts of sorbitol, 200 parts of flavoring agent, and 10 parts of bacteriostatic agent.

[0022] Example 3

[0023] 0.1 part of eldecalcitol, 500 parts of polyoxyethylene hydrogenated castor oil, 500 parts of medium-chain triglycerides, 1 part of tocopherol, 2000 parts of ethanol, 10000 parts of purified water, 1 part of citric acid, 5000 parts of sorbitol, 50 parts of flavoring agent, and 2 parts of bacteriostatic agent.

[0024] Example 4

[0025] An oral liquid preparation containing eldecalcitol is provided, comprising the following components in parts by weight: 0.01 part of eldecalcitol, 3000 parts of medium-chain triglycerides, and 50 parts of tocopherol.

[0026] Pharmacodynamic study on the treatment of osteoporosis induced by bilateral ovariectomy

[0027] Experimental animals

[0028] Healthy female SD rats, 10 - 12 weeks old, weighing 250 ± 20 g. After the rats were acclimatized in this laboratory for 1 week, they were randomly divided into 5 groups according to body weight, with 10 rats in each group. Specifically, there were 3 example groups (Examples 1 - 3), 1 model control group, and 1 normal control group: Except for the normal control group, osteoporosis models were established in all the other rats by bilateral ovariectomy.

[0029] During the model construction process, rats in each group were continuously administered by gavage for 12 weeks. Among them, the normal control group and the model control group were given 0.4 g / kg of normal saline by gavage every day, while the rats in the other groups were respectively given 3 mL / kg of the oral liquid of Examples 1-3 by gavage every day;

[0030] After 12 weeks of gavage administration, the rats were sacrificed, and the bone mineral density of the lumbar vertebrae and femurs of each rat was measured using a dual-energy X-ray bone densitometry body composition analyzer, and the bone calcium content of the femur was measured. The serum alkaline phosphatase activity was measured by colorimetry. The measurement results are shown in the following table.

[0031] Among them, the bone mineral density and bone calcium content of each group of rats are shown in Tables 1 and 2.

[0032] Table 1 Bone Mineral Density Content of Each Group

[0033] Group <![CDATA[Bone density (g / cm 3 )]]> Normal control group 0.165±0.002 Model control group 0.083±0.004 Example 1 0.151±0.001 Example 2 0.150±0.011 Example 3 0.148±0.010 Example 4 0.156±0.025

[0034] Table 2 Bone Calcium Content of Each Group

[0035] Group Bone calcium (%) Normal control group 9.63±1.13 Model control group 5.86±2.19 Example 1 9.18±1.60 Example 2 9.22±2.35 Example 3 9.20±1.87 Example 4 9.25±1.29

[0036] From the data in Tables 1 and 2, it can be seen that after taking the oral liquid of Examples 1-4, the osteoporosis symptoms of the rats were significantly improved, which was mainly reflected in the significant increase in the bone mineral density and bone calcium content of the rats, gradually approaching that of the normal control group, indicating that the oral liquid of this application has a better therapeutic effect on postmenopausal osteoporosis.

[0037] Among them, the serum alkaline phosphatase activity content of each group of rats is shown in Table 3.

[0038] Table 3 Serum Alkaline Phosphatase Activity of Each Group

[0039] Group AKP (King unit / 100 ml) Normal control group 10.672±1.563 Model control group 6.586±1.255 Example 1 10.128±1.422 Example 2 10.056±1.986 Example 3 10.091±1.768 Example 4 10.502±2.161

[0040] From the data in Table 3, it can be seen that: after taking the oral liquid of Examples 1-4, the serum alkaline phosphatase activity (AKP) of the rats increased significantly, indicating an increase in osteoblast activity and promoting osteoblast mineralization, which is helpful to significantly improve the osteoporosis situation.

[0041] Although the embodiments of the present invention have been disclosed as above, it is not limited to the applications listed in the specification and embodiments. It can be fully applied to various fields suitable for the present invention. For those familiar with the field, additional modifications can be easily made. Therefore, without departing from the general concept defined by the claims and the equivalent scope, the present invention is not limited to the specific details and the embodiments shown and described here.

Claims

1. An oral liquid preparation containing eldecalcitol, characterized in that, It is prepared from the following components: eldecalcitol, polyoxyethylene hydrogenated castor oil, medium-chain triglyceride, tocopherol, ethanol, purified water, citric acid or its salt, sorbitol, flavoring agent and bacteriostatic agent.

2. The oral liquid preparation containing eldecalcitol according to claim 1, characterized in that, It is prepared from the following components by weight: 0.01 - 0.1 part of eldecalcitol, 100 - 3000 parts of polyoxyethylene hydrogenated castor oil, 100 - 3000 parts of medium-chain triglyceride, 0.1 - 50 parts of tocopherol, 1000 - 3000 parts of ethanol, 5000 - 15000 parts of purified water, 50 - 200 parts of citric acid or its salt, 5000 - 10000 parts of sorbitol, 1 - 100 parts of flavoring agent and 1 - 10 parts of bacteriostatic agent.

3. The oral liquid preparation containing eldecalcitol according to claim 1, characterized in that, The bacteriostatic agent is any one or a combination of more than one of methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate.

4. The oral liquid preparation containing eldecalcitol according to claim 1, characterized in that, The flavoring agent is any one or a combination of more than one of sucrose, sorbitol, xylitol, sucralose, aspartame.

5. The oral liquid preparation containing eldecalcitol according to claim 1, characterized in that, The dosage form of the oral liquid preparation containing eldecalcitol is selected from at least one of drops, syrup, oral emulsion, oral suspension or oral solution.

6. The preparation method of the oral liquid preparation containing eldecalcitol according to any one of claims 1-4, characterized in that, It includes the following steps: Step S1: Take 1 / 2 of the above-mentioned parts by weight of citric acid or its salt, sorbitol, flavoring agent, bacteriostatic agent and purified water and mix them to obtain a first solution; Step S2: Take eldecalcitol, polyoxyethylene hydrogenated castor oil and / or medium-chain triglyceride, tocopherol and ethanol, mix them, and add the remaining purified water thereto to obtain a second solution; Step S3: Mix the first solution and the second solution, adjust the pH value to 6 - 8 with a pH regulator, then filter and sterilize to obtain a sterile medicinal liquid, and finally package it to obtain the target oral liquid preparation.