CN111956812A - Pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis - Google Patents

Pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis Download PDF

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CN111956812A
CN111956812A CN202010828154.5A CN202010828154A CN111956812A CN 111956812 A CN111956812 A CN 111956812A CN 202010828154 A CN202010828154 A CN 202010828154A CN 111956812 A CN111956812 A CN 111956812A
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nitric oxide
treatment
gastritis
pharmaceutical preparation
liquid matrix
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CN111956812B (en
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赵应征
鲁翠涛
肖健
张宏宇
林丽
黄志伟
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Wenzhou Medical University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1841—Transforming growth factor [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Gastroenterology & Hepatology (AREA)
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  • Acoustics & Sound (AREA)
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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract

The invention relates to a pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis, which comprises a liquid matrix and nitric oxide microbubbles, wherein the nitric oxide microbubbles are uniformly dispersed in the liquid matrix. The liquid matrix consists of xylitol, sodium carboxymethylcellulose and transforming growth factor-beta, the mass ratio of the xylitol to the sodium carboxymethylcellulose is 1-5: 10, and the concentration of the transforming growth factor-beta in the liquid matrix is 10 mg/L. The nitric oxide microbubble is composed of a vesicle formed by wrapping nitric oxide gas by taking soybean phospholipid and poloxamer as vesicle membrane materials, the particle size range is 2-5 mu m, and the concentration is 6 multiplied by 106～8×106one/mL. The medicinal preparation is used for ultrasonic diagnosis and treatment of gastritis after being orally taken.

Description

Pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis
Technical Field
The invention relates to an in-situ preparation for diagnosing and treating gastritis, in particular to a pharmaceutical preparation for ultrasonically diagnosing and treating gastritis.
Background
The research finds that the nitric oxide has good treatment potential on the inflammation. Through animal experiments of inflammation models, nitric oxide mainly plays an anti-inflammatory role in the initial stage of inflammation, and the specific roles comprise: maintaining microcirculation integrity, relaxing vascular smooth muscle, increasing intestinal mucosa blood flow, inhibiting adhesion and accumulation of platelets and leukocytes on the surface of endothelial cells, preventing thrombosis, inhibiting myeloperoxidase activity, protecting epithelial barrier, and promoting repair of epithelial tissue.
Nitric oxide plays a dual role in the progression of inflammation, both its protective role and its killing toxicity and pro-inflammatory effects, depending mainly on the site, amount and duration of nitric oxide production. In the hypoxic gastric environment, nitric oxide exerts mainly anti-inflammatory and gastric protective effects. Most of the reported methods for supplementing nitric oxide in vivo have been the use of nitric oxide donor compounds. Nitric oxide donor compounds fall into two classes: non-enzymogenic and enzymogenic forms. Most of non-enzymatic nitric oxide donor compounds come from nitro compounds, including nitroprusside, organic or inorganic nitrite and nitrate, nitrosamine, nitrogen mustard, hydrazine and the like, and have small dosage and large toxic and side effects. The enzymatic nitric oxide donor compound (such as arginine) needs to be decomposed by in vivo biological enzymes to produce nitric oxide molecules. The nitric oxide molecules generated by the above nitric oxide donor compounds cannot be concentrated in the stomach for acting, so the diagnosis and treatment of gastritis by using the nitric oxide donor compounds are poor.
The oral medicine preparation has the advantages of convenient taking, quick absorption and quick effect taking, and is easily accepted by patients. The nitric oxide molecule is in gaseous form, and nitric oxide gas (NO) is slightly soluble in water, and has a solubility of only 5.6X 10 in water at 20 deg.C-3g/L (equivalent to 0.186. mu. mol/L), and cannot be directly prepared into oral pharmaceutical preparations.
Therefore, nitric oxide has a good treatment potential on gastritis, but nitric oxide is a gas, and no research report that nitric oxide can be efficiently carried in oral pharmaceutical preparations is found at present. Therefore, the preparation of oral pharmaceutical preparations carrying nitric oxide gas with high efficiency is a limiting bottleneck in exerting the effect of nitric oxide for ultrasonic diagnosis and treatment of gastritis.
Disclosure of Invention
The invention aims to overcome the defects of the prior art (namely, the lack of an oral pharmaceutical preparation carrying nitric oxide gas efficiently) and provide a pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis, so that the invention provides sufficient guarantee for ensuring the effective diagnosis and treatment of the nitric oxide and meets the requirements of clinical treatment on safety, effectiveness, convenience and economy.
The inventor finds that soybean phospholipid and poloxamer, which are 2-5 mu m microbubbles formed by wrapping nitrogen monoxide with a bubble film material, have good ultrasonic imaging and cavitation blasting effects at the same time, and can be used as an effective preparation for ultrasonic imaging and treatment of gastritis. In addition, transforming growth factor-beta (TGF-beta) and nitric oxide molecules work synergistically to increase the efficacy of the treatment of gastritis.
Through a large number of experiments, the invention obtains the medicinal preparation capable of ultrasonically diagnosing and treating the gastritis, and the medicinal preparation comprises a liquid matrix and nitric oxide microbubbles, wherein the nitric oxide microbubbles are uniformly dispersed in the liquid matrix.
The liquid matrix is composed of xylitol, sodium carboxymethylcellulose and transforming growth factor-beta.
The mass ratio of the xylitol to the sodium carboxymethylcellulose in the liquid matrix is 1-5: 10, and the concentration of the transforming growth factor-beta in the liquid matrix is 10 mg/L.
The liquid matrix is further added with: flavoring agents, pH buffers, antibacterial agents, antioxidants, and therapeutic agents.
The nitric oxide microbubble is composed of a vesicle formed by wrapping nitric oxide gas by taking soybean phospholipid and poloxamer as vesicle membrane materials.
The particle size of the nitric oxide microbubbles is 2 to 5 μm.
The concentration of the nitric oxide microvesicle in the pharmaceutical preparation is 6 × 106～8×106one/mL.
The preparation method of the medicinal preparation for ultrasonic diagnosis and treatment of gastritis is characterized by comprising the following steps of:
a: dispersing the liquid matrix component in 10 times of 8 ℃ injection water by mass, placing the mixture in a refrigerator at 4-8 ℃ overnight, and slowly dissolving the mixture to form a liquid matrix solution;
b: mixing soybean phospholipid and poloxamer in a mass ratio of 1: 25, dissolving the mixture in anhydrous tert-butyl alcohol with the mass of 10 times of that of 65 ℃, slowly cooling the mixture until the solution is solidified, standing the mixture overnight at the temperature of-10 ℃, freeze-drying the mixture to obtain loose freeze-dried powder, transferring the loose freeze-dried powder into a bottle with a plug, filling nitric oxide gas into the bottle until the nitric oxide gas is saturated, adding water for injection with the mass of 5 times of the freeze-dried powder, and uniformly mixing the mixture to form nitric oxide microbubble solution;
c: adding the nitric oxide microbubble solution prepared in the step b into the liquid matrix solution prepared in the step a at the temperature of 10 ℃ until the concentration of the nitric oxide microbubbles in the pharmaceutical preparation is 6 multiplied by 106～8×106And (4) shaking lightly and mixing uniformly to prepare a medicinal preparation for ultrasonic diagnosis and gastritis treatment, and storing in a sealed environment at 15-20 ℃.
The liquid matrix solution described above is further added with: flavoring agents, pH buffers, antibacterial agents, antioxidants, and therapeutic agents.
The medicinal preparation is used for ultrasonic diagnosis and treatment of gastritis after being orally taken.
The pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis of the invention has the following advantages: the medicinal preparation for ultrasonic diagnosis and treatment of gastritis has the functions of biological adhesion in stomach and slow release and long-acting effect, and has good affinity and biocompatibility to gastric epithelial mucosa; the pharmaceutical preparation for ultrasonic diagnosis and gastritis treatment does not use any nitric oxide donor compound, and does not generate adverse reaction and toxic or side effect on body tissues because of the nitric oxide donor compound; the medicinal preparation is convenient to use, and is adhered to the surface of the stomach wall immediately after entering the stomach by oral administration, so that the ultrasonic diagnosis and treatment of the gastritis are realized; fourthly, the storage and the transportation of the medicinal preparation are convenient.
Detailed Description
Hereinafter, specific embodiments of the present invention will be described in detail. It should be noted that technical features or combinations of technical features described in the following embodiments should not be considered as being isolated, and they may be combined with each other to achieve better technical effects.
EXAMPLE 1 preparation of pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis
The pharmaceutical preparation for ultrasonic diagnosis and gastritis treatment of the experimental group is prepared according to the component proportion of the table 1, and the pharmaceutical preparation specifically comprises the following steps:
a: dispersing each component of the liquid matrix in 10 times of the mass of 8 ℃ injection water, placing the mixture in a refrigerator at 4-8 ℃ overnight, and slowly dissolving the mixture to form a liquid matrix solution;
b: mixing soybean phospholipid and poloxamer in a mass ratio of 1: 25, dissolving the mixture in anhydrous tert-butyl alcohol with the mass of 10 times of that of 65 ℃, slowly cooling the mixture until the solution is solidified, standing the mixture overnight at the temperature of-10 ℃, freeze-drying the mixture to obtain loose freeze-dried powder, transferring the loose freeze-dried powder into a bottle with a plug, filling nitric oxide gas into the bottle until the nitric oxide gas is saturated, adding water for injection with the mass of 5 times of the freeze-dried powder, and uniformly mixing the mixture to form nitric oxide microbubble solution;
c: and (c) adding the nitric oxide microbubble solution prepared in the step (b) into the liquid matrix solution prepared in the step (a) at the temperature of 10 ℃, adjusting the concentration of the nitric oxide microbubbles in the medicinal preparation according to the design shown in the table 1, shaking gently and mixing uniformly to prepare the medicinal preparation for ultrasonic diagnosis and gastritis treatment, and storing in a sealed environment at the temperature of 15-20 ℃.
Control formulations were prepared with reference to the experimental group according to the component ratios of table 1. The experimental groups are configured according to the components and the proportion within the protection scope of the claims of the application, and the control groups are the deletion of a certain component or the mass percentage of the component beyond the protection scope of the claims of the application.
TABLE 1 compositions of the pharmaceutical preparations of the experimental and control groups
Figure BSA0000216975280000031
Figure BSA0000216975280000041
Note: "√" represents the term prepared according to the concentrations and methods of the experimental group of example 1; "/" indicates that the item is absent; represents that the component is replaced by the component in the parentheses of the component; PG represents a prostaglandin; NO represents nitric oxide gas; o is2Represents oxygen; n is a radical of2Representing nitrogen.
EXAMPLE 2 pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis
(1) Establishment of gastritis model animal
Male SD rats with the body weight of 180-. The abdominal skin of the rat was disinfected with 0.5% iodophor, the abdomen was opened along the lower edge of the left rib, and the stomach was gently pulled out. The gastric ulcer preparation forceps (patent No.: ZL2009200151947) were used to clamp the area of the stomach 3mm from the pylorus, the needle of a syringe which had previously been filled with 0.18mL of mineral oil and 0.02mL of 60% acetic acid was inserted into the stomach cavity of the clamping region, 0.18mL of mineral oil and 0.02mL of 60% acetic acid were injected into the stomach cavity of the clamping region, acetic acid was aspirated from the stomach after 45 seconds, 2mL of physiological saline was injected into the stomach cavity, and the reaction was stopped after 1 min. Resetting the stomach, dripping 0.1mL of penicillin sodium injection (80 ten thousand units of penicillin sodium is added into 4mL of normal saline and mixed evenly) into the incision, and closing the abdomen layer by layer. Postoperative rats were fasted and had free access to oral rehydration salt. The intraoperative procedure was gently kneaded and aseptic manipulation was noted to reduce adhesions. After 12 days, an ELASA detection kit is used for detecting the IL-8 level of serum, and when the IL-8 level is obviously higher than that of a normal rat, the establishment of a gastritis model animal is proved to be successful.
(2) Ultrasonic diagnosis of various groups of medicinal preparations and effect of treating gastritis
Selecting rats successfully modeled after gastritis, averagely dividing the rats into a plurality of groups according to the design of table 1, performing intragastric administration for 1mL in 1, 3, 5, 7 and 9 days, then performing ultrasonic examination on the stomach by using a small animal ultrasonic imaging instrument, reserving images, performing euthanasia on the animals after 12 days of conventional feeding, observing the pathophysiological conditions of the stomach part through histological staining, particularly observing whether edema, ulcer and other conditions occur in mucous membrane and lower tissues thereof, and comprehensively evaluating the diagnosis effect of each group of medicinal preparations and the gastritis treatment effect.
The evaluation results of the groups are shown in table 2, and the total scores of the application effects of the medicinal preparations of the groups are given by integrating the evaluation indexes.
TABLE 2 ultrasonic diagnosis and therapeutic effect of the drug preparations of the experimental group and the control group on gastritis
Group of Ultrasound image Level of stomach wall Gastric mucosa and its underlying tissue Total score
Experimental group 1 Clear and strong echo Complete without abnormal conditions Is returned to normal 86
Experimental group 2 Clear and strong echo Complete without abnormal conditions Is returned to normal 88
Experimental group 3 Clear and strong echo Complete without abnormal conditions Is returned to normal 94
Experimental group 4 Clear and strong echo Complete without abnormal conditions Is returned to normal 92
Experimental group 5 Clear and strong echo Complete without abnormal conditions Is returned to normal 91
Experimental group 6 Clear and strong echo Complete without abnormal conditions Is returned to normal 96
Control group 1 Fuzzy, weak echo Disorder of the heart Marked edema and ulcer 15
Control group 2 No image Disorder of the heart Marked edema and ulcer 10
Control group 3 No image Disorder of the heart Marked edema and ulcer 11
Control group 4 Clear and strong echo Is relatively complete and close to normal Near normal 52
Control group 5 Clear and strong echo Is relatively complete and close to normal Near normal 54
Control group 6 Clear and strong echo Is relatively complete and close to normal Near normal 52
Control group 7 Clear and strong echo Some confusion Visible edema and ulceration 38
Control group 8 Clear and strong echo Some confusion Visible edema and ulceration 32
Control group 9 Clear and strong echo Some confusion Visible edema and ulceration 28
Control group 10 Clear and strong echo Is relatively complete and close to normal Near normal 48
Control group 11 Slightly blurred and weak echo Some confusion Visible edema and ulceration 31
Control group 12 Fuzzy, weak echo Some confusion Visible edema and ulceration 25
Control group 13 Slightly blurred and weak echo Is relatively complete and close to normal Near normal 38
Control group 14 Clear and strong echo Disorder of the heart Marked edema and ulcer 10
Control group 15 Clear and strong echo Disorder of the heart Marked edema and ulcer 10
Control group 16 Slightly blurred and weak echo Is relatively complete and close to normal Near normal 41
Control group 17 Fuzzy, strong echo Is relatively complete and close to normal Near normal 40
Control group 18 Slightly fuzzy and strong echo Is relatively complete and close to normal Near normal 38
Control group 19 Virtual image, echo clutter Is relatively complete and close to normal Near normal 34
As can be seen from the experimental results in Table 2, the experimental group has good ultrasonic diagnosis and treatment effects on gastritis, particularly the experimental group 6 has clear ultrasonic images, complete stomach wall layers, normal stomach mucosa and lower tissues thereof and good ultrasonic diagnosis and treatment effects on gastritis. Compared with the experimental group, the control group has obviously poor ultrasonic diagnosis and treatment effects on the gastritis, particularly the control groups 1, 2, 3, 5, 14 and 15 have poor ultrasonic diagnosis or treatment effects on the gastritis, and the control group 5 has effective ultrasonic diagnosis or treatment effects on the gastritis but is not suitable for the diabetic patients.
The experimental results in table 2 prove that any component and condition in the technical protection scheme of the present invention are synergistic and indispensable, and that any component and condition in the technical protection scheme of the present invention will have an obvious effect on the ultrasonic diagnosis and treatment effect of gastritis. The medicinal preparation has good ultrasonic diagnosis and treatment effects on gastritis, and has good application prospect.
The above detailed description is specific to possible embodiments of the invention, and the embodiments are not intended to limit the scope of the invention, and all equivalent implementations or modifications that do not depart from the scope of the invention should be construed as being included within the scope of the invention. In addition, various modifications, additions and substitutions in other forms and details may occur to those skilled in the art within the scope and spirit of the invention as disclosed in the claims. It is understood that various modifications, additions, substitutions and the like can be made without departing from the spirit of the invention as disclosed in the accompanying claims.

Claims (10)

1. The medicinal preparation for ultrasonic diagnosis and treatment of gastritis is mainly characterized in that: the pharmaceutical preparation comprises a liquid matrix and nitric oxide microbubbles, wherein the nitric oxide microbubbles are uniformly dispersed in the liquid matrix.
2. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 1, characterized in that: the liquid matrix consists of xylitol, sodium carboxymethyl cellulose and transforming growth factor-beta.
3. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 2, characterized in that: the mass ratio of the xylitol to the sodium carboxymethylcellulose in the liquid matrix is 1-5: 10, and the concentration of the transforming growth factor-beta in the liquid matrix is 10 mg/L.
4. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 2, characterized in that: the liquid matrix is further added with: flavoring agents, pH buffers, antibacterial agents, antioxidants, and therapeutic agents.
5. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 1, characterized in that: the nitric oxide microbubble is composed of a vesicle formed by wrapping nitric oxide gas by taking soybean phospholipid and poloxamer as vesicle membrane materials.
6. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 1, characterized in that: the particle size range of the nitric oxide microbubbles is 2-5 microns.
7. The pharmaceutical preparation for ultrasound diagnosis and treatment of gastritis according to claim 1, characterized in that: the concentration of the nitric oxide microvesicle in a pharmaceutical preparation is 6 x 106～8×106one/mL.
8. A method for preparing a pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis according to claim 1, characterized by comprising the steps of:
a: dispersing the liquid matrix component in 10 times of 8 ℃ injection water by mass, placing the mixture in a refrigerator at 4-8 ℃ overnight, and slowly dissolving the mixture to form a liquid matrix solution;
b: mixing soybean phospholipid and poloxamer in a mass ratio of 1: 25, dissolving in anhydrous tert-butyl alcohol of 10 times the mass of 65 ℃, slowly cooling until the solution is solidified, standing overnight at-10 ℃, freeze-drying to obtain loose freeze-dried powder, transferring into a bottle with a plug, filling nitric oxide gas until the nitric oxide gas is saturated, adding water for injection of 5 times the mass of the freeze-dried powder, and uniformly mixing to form a nitric oxide microbubble solution;
c: adding the nitric oxide microbubble solution prepared in the step b into the liquid matrix solution prepared in the step a at the temperature of 10 ℃ until the concentration of the nitric oxide microbubbles in the pharmaceutical preparation is 6 multiplied by 106～8×106And (4) shaking lightly and mixing uniformly to prepare a medicinal preparation for ultrasonic diagnosis and gastritis treatment, and storing in a sealed environment at 15-20 ℃.
9. A process for the preparation of a pharmaceutical preparation for use in the ultrasonic diagnosis and treatment of gastritis according to claim 8, characterized in that: the liquid matrix solution is further added with: flavoring agents, pH buffers, antibacterial agents, antioxidants, and therapeutic agents.
10. The pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis according to claim 1, characterized in that: the medicinal preparation is used for ultrasonic diagnosis and treatment of gastritis after being orally taken.
CN202010828154.5A 2020-08-06 2020-08-06 Pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis Active CN111956812B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101195029A (en) * 2006-12-06 2008-06-11 姜广良 Application method of nitric oxide donator in enteron mucosal disease
US20140079679A1 (en) * 2012-09-19 2014-03-20 Transdermal Biotechnology, Inc. Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery
CN111228466A (en) * 2020-02-27 2020-06-05 温州医科大学 Hydrogel containing oxygen microbubbles for treating diabetic foot, and preparation method and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101195029A (en) * 2006-12-06 2008-06-11 姜广良 Application method of nitric oxide donator in enteron mucosal disease
US20140079679A1 (en) * 2012-09-19 2014-03-20 Transdermal Biotechnology, Inc. Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery
CN111228466A (en) * 2020-02-27 2020-06-05 温州医科大学 Hydrogel containing oxygen microbubbles for treating diabetic foot, and preparation method and application thereof

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