CN110327471B - Antispasmodic agent for endoscopy and preparation method thereof - Google Patents

Antispasmodic agent for endoscopy and preparation method thereof Download PDF

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CN110327471B
CN110327471B CN201910677597.6A CN201910677597A CN110327471B CN 110327471 B CN110327471 B CN 110327471B CN 201910677597 A CN201910677597 A CN 201910677597A CN 110327471 B CN110327471 B CN 110327471B
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parts
weight
antifoaming agent
ultrasonic
defoaming
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李苏
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Beijing Yiliya Medical Technology Co.,Ltd.
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Onas Beijing Pharmaceutical Technology Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system

Abstract

The invention provides an endoscopic spasmolysis defoaming agent and a preparation method thereof, wherein the defoaming agent comprises 1-3 parts of L-menthol, 0.5-1 part of surfactant, 0.05-0.1 part of defoaming agent and 65-75 parts of purified water.

Description

Antispasmodic agent for endoscopy and preparation method thereof
Technical Field
The invention belongs to the field of preparations for endoscopy, and particularly relates to a spasmolytic antifoaming agent for endoscopy and a preparation method thereof.
Background
High-definition endoscopes are often used for examining the disease focus condition in the gastrointestinal tract in medical treatment, however, mucus and foam in the gastrointestinal tract often affect the visual field of the endoscope, so that the detection rate of tiny disease focus is low, and the examination time is prolonged; excessive contraction of the gastrointestinal tract may then prevent proper diagnosis and may allow minor lesions, such as small-sized cancerous sites, to be missed.
In order to solve the above problems during endoscopy, CN1893982A discloses a menthol-containing formulation which is an emulsion containing L-menthol, a surfactant and an antifoaming agent, is used for inhibiting smooth muscle contraction, and can maintain stability for a long time, exhibiting high light transmittance. However, the content of the defoaming agent in the emulsion is low, and if the content of the defoaming agent is increased, the solubility of the defoaming agent is lowered, and the defoaming agent precipitates from the emulsion, and the defoaming agent in the emulsion is only used for eliminating bubbles existing during the use of the emulsion, and cannot eliminate bubbles existing in gastric juice.
Disclosure of Invention
In order to solve the technical problems, the invention provides the defoaming agent special for endoscopy, and the defoaming agent can be used independently, has a defoaming effect and also has good light transmittance.
The specific technical scheme of the invention is as follows:
the invention provides a spasmolytic defoaming agent for endoscopy, which comprises the following components in parts by weight:
l-menthol 1-3 surfactant 0.5-1
0.05-0.1 of defoaming component and 65-75 of purified water.
In a further improvement, the defoaming component is a mixture of 0.02-0.04 parts of sodium cholate and 0.03-0.06 parts of polydimethylsiloxane.
In a further improvement, the sodium cholate and the polydimethylsiloxane form a dispersion, and the dispersion is prepared by the following method: placing sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 20-30min at the rotation speed of 500rpm, reversely continuing grinding for 20-30min at the rotation speed of 500rpm, taking out, and sieving with a 120-mesh sieve to obtain the dispersion.
In a further improvement, the surfactant comprises the following components in parts by weight:
polyethylene glycol 15000.05-0.2 octadecyl trimethyl ammonium chloride 0.35-0.5
Sodium lactate 0.1-0.3.
In a further improvement, the defoaming agent also comprises 1-3 parts by weight of liquiritigenin.
The invention also provides a preparation method of the spasmolytic antifoaming agent for endoscopy, which comprises the following steps: adding surfactant into purified water, stirring at 500rpm for 7min, standing, adding L-menthol and defoaming component into the above solution, and performing ultrasonic treatment to obtain defoaming agent.
Preferably, the conditions of the ultrasound are: 15-20 ℃, the ultrasonic power is 65-75w, the ultrasonic time is 3-5s, the interval time is 4-5s, and the cumulative ultrasonic time is 30-35 min.
The invention provides a spasmolytic defoaming agent for endoscopy, which has very good foam inhibition capability in gastrointestinal environment, high defoaming speed and light transmittance remarkably superior to that of the existing emulsion and defoaming agent.
Detailed Description
Example 1
Figure GDA0003131889670000031
Example 2
Figure GDA0003131889670000032
The sodium cholate and the polydimethylsiloxane form a dispersion, and the preparation method of the dispersion comprises the following steps: and (2) placing the sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 20min at the rotating speed of 500rpm, reversely continuing grinding for 20min at the rotating speed of 500rpm, taking out, and sieving by a 120-mesh sieve to obtain the dispersion.
Example 3
Figure GDA0003131889670000033
Figure GDA0003131889670000041
The preparation method of the spasmolytic antifoaming agent for endoscopy comprises the following steps:
adding polyethylene glycol 1500, octadecyl trimethyl ammonium chloride and sodium lactate into purified water, stirring at 500rpm for 7min, standing, adding L-menthol and sodium cholate and polydimethylsiloxane into the above solution, and performing ultrasonic treatment to obtain defoaming agent under the following conditions: the ultrasonic temperature is 15 ℃, the ultrasonic power is 65w, the ultrasonic time is 5s, the interval time is 4s, and the cumulative ultrasonic time is 35 min.
Example 4
Figure GDA0003131889670000042
The sodium cholate and the polydimethylsiloxane form a dispersion, and the preparation method of the dispersion comprises the following steps: placing sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 30min at the rotation speed of 500rpm, reversely continuing grinding for 30min at the rotation speed of 500rpm, taking out, and sieving with a 120-mesh sieve to obtain the dispersion.
The preparation method of the spasmolytic antifoaming agent for endoscopy comprises the following steps:
adding polyethylene glycol 1500, octadecyl trimethyl ammonium chloride and sodium lactate into purified water, stirring at 500rpm for 7min, standing, adding L-menthol and the dispersion into the solution, and performing ultrasonic treatment to obtain defoaming agent, wherein the ultrasonic treatment conditions are as follows: the ultrasonic temperature is 20 ℃, the ultrasonic power is 75w, the ultrasonic time is 3s, the interval time is 4s, and the cumulative ultrasonic time is 30 min.
Example 5
Figure GDA0003131889670000051
Example 6
Figure GDA0003131889670000052
Figure GDA0003131889670000061
Example 7
Figure GDA0003131889670000062
The preparation method of the spasmolytic antifoaming agent for endoscopy comprises the following steps:
adding polyethylene glycol 1500, octadecyl trimethyl ammonium chloride and sodium lactate into purified water, stirring at 500rpm for 7min, standing, adding L-menthol, sorbitol, polyacrylic acid, carbomer, sodium cholate and polydimethylsiloxane into the above solution, and performing ultrasonic treatment to obtain defoaming agent under the following conditions: the ultrasonic temperature is 17 ℃, the ultrasonic power is 70w, the ultrasonic time is 4s, the interval time is 5s, and the cumulative ultrasonic time is 35 min.
Example 8
Figure GDA0003131889670000071
The sodium cholate and the polydimethylsiloxane form a dispersion, and the preparation method of the dispersion comprises the following steps: placing sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 30min at the rotation speed of 500rpm, reversely continuing grinding for 30min at the rotation speed of 500rpm, taking out, and sieving with a 120-mesh sieve to obtain the dispersion.
The preparation method of the spasmolytic antifoaming agent for endoscopy comprises the following steps:
adding polyethylene glycol 1500, octadecyl trimethyl ammonium chloride and sodium lactate into purified water, stirring at 500rpm for 7min, standing, adding L-menthol, sorbitol, polyacrylic acid, carbomer, and dispersoid into the above solution, and performing ultrasonic treatment to obtain defoaming agent, wherein the ultrasonic treatment conditions are as follows: the ultrasonic temperature is 16 ℃, the ultrasonic power is 68w, the ultrasonic time is 4s, the interval time is 5s, and the cumulative ultrasonic time is 35 min.
Example 9
Figure GDA0003131889670000081
The sodium cholate and the polydimethylsiloxane form a dispersion, and the preparation method of the dispersion comprises the following steps: placing sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 30min at the rotation speed of 500rpm, reversely continuing grinding for 30min at the rotation speed of 500rpm, taking out, and sieving with a 120-mesh sieve to obtain the dispersion.
The preparation method of the spasmolytic antifoaming agent for endoscopy comprises the following steps:
adding polyethylene glycol 1500, octadecyl trimethyl ammonium chloride and sodium lactate into purified water, stirring at 500rpm for 7min, standing, adding L-menthol and dispersoid and glycyrrhizin into the above solution, and performing ultrasonic treatment to obtain defoaming agent, wherein the ultrasonic conditions are as follows: the ultrasonic temperature is 20 ℃, the ultrasonic power is 75w, the ultrasonic time is 3s, the interval time is 4s, and the cumulative ultrasonic time is 30 min.
Example 10
Figure GDA0003131889670000082
Figure GDA0003131889670000091
The preparation method is the same as example 9.
Example 11
Figure GDA0003131889670000092
The preparation method is the same as example 9.
Comparative example 1
CN1893982A emulsion disclosed in example 1.
Comparative example 2
Figure GDA0003131889670000093
Figure GDA0003131889670000101
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that in example 3.
Comparative example 3
Figure GDA0003131889670000102
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that in example 3.
Comparative example 4
Figure GDA0003131889670000103
Figure GDA0003131889670000111
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that in example 3.
Comparative example 5
Figure GDA0003131889670000112
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that in example 3.
Comparative example 6
Figure GDA0003131889670000113
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that in example 3.
Comparative example 7
Figure GDA0003131889670000121
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that of example 5.
Comparative example 8
Figure GDA0003131889670000122
Figure GDA0003131889670000131
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that of example 5.
Comparative example 9
Figure GDA0003131889670000132
The preparation method of the spasmolytic antifoaming agent for endoscopy is the same as that of example 5.
Comparative example 10
Figure GDA0003131889670000133
Figure GDA0003131889670000141
The preparation method is the same as example 9.
Comparative example 11
Figure GDA0003131889670000142
The preparation method is the same as example 9.
Comparative example 12
Figure GDA0003131889670000143
Figure GDA0003131889670000151
The preparation method is the same as example 9.
Experimental example 1 defoaming Capacity test
Preparing artificial gastric juice and artificial intestinal juice according to the method in annex XA of the second part of Chinese pharmacopoeia 2010:
artificial gastric juice: taking 16.4mL of dilute hydrochloric acid, adding about 800mL of water and 10g of pepsin, shaking up, and adding water to dilute into 1000mL to obtain the finished product.
Artificial intestinal juice: namely phosphate buffer (containing pancreatin) (pH 6.8).
Dividing 30mL bottles into four groups, and placing 10mL of artificial gastric juice in each bottle of the first group and the second group; the bottles of the third and fourth groups were filled with 10mL of artificial intestinal juice, then 10mL of the antifoaming agent provided in the examples and comparative examples of the present invention was placed in the first and third groups at 25 ℃ and 10mL of the antifoaming agent provided in the examples and comparative examples of the present invention was placed in the second and fourth groups at 37 ℃, the temperature of each group was maintained, the mixture was shaken on a shaker (200r/min) for 1min, and after 1min, the foam disappearance time T and the light transmittance Y were measured, and the results are shown in Table 1.
TABLE 1 defoaming Capacity test results of examples and comparative examples
Figure GDA0003131889670000152
As can be seen from the table, the anti-spasm agent for endoscopy provided by the present invention has a light transmittance significantly better than that of the control group when detected in the artificial gastric juice or the artificial intestinal juice at 25 ℃ or 37 ℃, and the defoaming time is significantly lower than that of the control group, and from the experimental data of the control example 1, the emulsion provided by the control example 1 has a good light transmittance at a pH of 7 and a temperature of 25 ℃, and the defoaming time is short, and when detected in the artificial gastric juice or the artificial gastric juice at 37 ℃, the light transmittance is significantly lower than that of the anti-spasm agent provided by the present application, and the defoaming time is significantly prolonged. And as can be seen from the above table, the defoaming component significantly affects the defoaming time, and the surfactant significantly affects the light transmittance.
Therefore, when the endoscopic spasmolysis defoaming agent provided by the invention is used for gastrointestinal endoscopy, the gastrointestinal endoscopy light transmittance can be obviously improved, and the defoaming time can be obviously shortened.
Experimental example 2 adsorption experiment
A protein solution having a gastrointestinal protein concentration of 1.0mg/mL was prepared using a phosphate buffer solution (pH6.8), and the antifoaming agents (microsphere content of 0.3g) of the examples and comparative examples provided in the present invention were added to a test tube containing the protein solution (0.3mL), respectively, and shaken (120r/min) in a constant temperature shaker at 37 ℃ for 4 hours, and then the protein content in the solution was measured. The protein adsorption on the microspheres was calculated from the amount of protein before and after adsorption, and the protein adsorption rate (initial protein amount-4 h post protein amount)/initial protein amount 100%, and the adsorption rate for each group of proteins is shown in table 2.
TABLE 2 adsorption test results of examples and comparative examples
Sample (I) Adsorption Rate (%)
Example 7 45.6
Comparative example 7 0
Comparative example 8 2.3
Comparative example 9 8.3
As can be seen from the table, the defoaming agent provided by the invention has a certain adsorption effect on gastrointestinal proteins, so that the defoaming agent provided by the invention has a certain protein adsorption effect, can adsorb proteins adhered to the intestinal wall into the defoaming agent, further improves the definition of gastrointestinal examination, and improves the accuracy of examination.
EXAMPLE 3 spasm inhibition experiment
SD rats, body weight 200-;
rats were divided into 6 groups, 1 group for administration, 2 groups for administration, 1 group for control, 2 groups for control, 3 groups for control and blank control, and after fasting for 12 hours, the rats were administered as follows:
administration of 1 group 5mL of the antifoaming agent of example 1 of the present invention was administered by intragastric administration;
administration 2 groups 5mL of the antifoaming agent of example 9 of the present invention were intragastrically administered;
5mL of the antifoaming agent of comparative example 10 of the present invention was administered to the group of control 1 by gavage;
5mL of the antifoaming agent of comparative example 11 of the present invention was administered to the control group 2 by gavage;
5mL of the antifoaming agent of comparative example 12 of the present invention was administered to the control group 3 by gavage;
the blank control group was given an equal volume of saline.
Calculated using the conventional method, the inhibition ratio (%) was (average tension after KCl administration-average tension after administration)/(average tension after KCl administration-resting tension) x 100%, and the inhibition ratio results for each group are shown in table 3.
TABLE 3 results of spasm inhibition experiments in each group
Group of Inhibition ratio (%)
Blank control group 7.56±1.23
Administration of 1 group 65.94±2.37
Administration of 2 groups 90.68±5.66
Control 1 group 22.38±2.82
Control 2 group 60.32±1.57
Control 3 group 61.55±2.96
As can be seen from the table, the antifoaming agent provided by the embodiment of the present invention has a significant inhibitory effect on spasm of colon, and as can be seen from the table, glycyrrhizin and L-menthol have a synergistic effect.

Claims (5)

1. The antispasmodic agent for endoscopy is characterized by comprising the following components in parts by weight:
l-menthol 1-3 surfactant 0.5-1
0.05-0.1 of defoaming component and 65-75 of purified water;
the defoaming component is a mixture of 0.02-0.04 parts of sodium cholate and 0.03-0.06 parts of polydimethylsiloxane;
the sodium cholate and the polydimethylsiloxane form a dispersion, and the preparation method of the dispersion comprises the following steps: placing sodium cholate in a mortar, slowly adding polydimethylsiloxane while grinding, grinding for 20-30min at the rotation speed of 500rpm, reversely continuing to grind for 20-30min at the rotation speed of 500rpm, taking out, and sieving with a 120-mesh sieve to obtain a dispersion;
the surfactant comprises the following components in parts by weight:
polyethylene glycol 15000.05-0.2 octadecyl trimethyl ammonium chloride 0.35-0.5
Sodium lactate 0.1-0.3.
2. The endoscopic spasmolytic antifoaming agent according to claim 1, further comprising 0.01 to 0.05 parts by weight of sorbitol, 0.2 to 0.4 parts by weight of polyacrylic acid, and 0.7 to 1.2 parts by weight of carbomer.
3. The endoscopic spasmolytic antifoaming agent according to claim 1, wherein the antifoaming agent further comprises 1-3 parts by weight of liquiritigenin.
4. A method for preparing an endoscopic spasmolytic antifoaming agent according to claim 1, comprising the steps of: adding surfactant into purified water, stirring at 500rpm for 7min, standing, adding L-menthol and defoaming component into the above solution, and performing ultrasonic treatment to obtain defoaming agent.
5. The method of claim 4, wherein the sonication conditions are: the ultrasonic temperature is 15-20 ℃, the ultrasonic power is 65-75w, the ultrasonic time is 3-5s, the interval time is 4-5s, and the cumulative ultrasonic time is 30-35 min.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1893982A (en) * 2003-06-30 2007-01-10 日本制药株式会社 Menthol-containing preparation
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CN106177971A (en) * 2016-07-20 2016-12-07 贵州理工学院 Potato starch capsule shells containing menthol

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US20070148099A1 (en) * 2005-12-27 2007-06-28 Burke Susan E Use of aroma compounds as defoaming agents for ophthalmic solutions with high concentrations of surfactants

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Publication number Priority date Publication date Assignee Title
CN1893982A (en) * 2003-06-30 2007-01-10 日本制药株式会社 Menthol-containing preparation
CN102038963A (en) * 2003-06-30 2011-05-04 日本制药株式会社 Method for preparing a stabilised menthol emulsion
CN103110961A (en) * 2012-11-30 2013-05-22 江苏唯德康医疗科技有限公司 Preparation method of high-definition endoscope mucus-removal defoaming composite preparation
CN106177971A (en) * 2016-07-20 2016-12-07 贵州理工学院 Potato starch capsule shells containing menthol

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