CN113209314A - Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease - Google Patents
Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease Download PDFInfo
- Publication number
- CN113209314A CN113209314A CN202110492173.XA CN202110492173A CN113209314A CN 113209314 A CN113209314 A CN 113209314A CN 202110492173 A CN202110492173 A CN 202110492173A CN 113209314 A CN113209314 A CN 113209314A
- Authority
- CN
- China
- Prior art keywords
- chromogenic
- color developing
- oral capsule
- detecting
- reflux disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940100691 oral capsule Drugs 0.000 title claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 208000005206 Laryngopharyngeal Reflux Diseases 0.000 title claims description 19
- 206010067869 Reflux laryngitis Diseases 0.000 title claims description 19
- 210000003026 hypopharynx Anatomy 0.000 claims abstract description 35
- 239000002245 particle Substances 0.000 claims abstract description 30
- 239000002775 capsule Substances 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 22
- 239000002861 polymer material Substances 0.000 claims abstract description 13
- 229920006237 degradable polymer Polymers 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 239000011248 coating agent Substances 0.000 claims abstract description 6
- 238000000576 coating method Methods 0.000 claims abstract description 6
- 238000011049 filling Methods 0.000 claims abstract description 4
- 229960000907 methylthioninium chloride Drugs 0.000 claims description 30
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000004952 Polyamide Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- 229920002647 polyamide Polymers 0.000 claims description 10
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 7
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 6
- 238000012695 Interfacial polymerization Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- LXEJRKJRKIFVNY-UHFFFAOYSA-N terephthaloyl chloride Chemical compound ClC(=O)C1=CC=C(C(Cl)=O)C=C1 LXEJRKJRKIFVNY-UHFFFAOYSA-N 0.000 claims description 5
- 229930182559 Natural dye Natural products 0.000 claims description 3
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 238000004945 emulsification Methods 0.000 claims description 3
- 238000005538 encapsulation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007903 gelatin capsule Substances 0.000 claims description 3
- 238000010297 mechanical methods and process Methods 0.000 claims description 3
- 239000000978 natural dye Substances 0.000 claims description 3
- 238000005191 phase separation Methods 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920002379 silicone rubber Polymers 0.000 claims description 3
- 239000004945 silicone rubber Substances 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 239000000979 synthetic dye Substances 0.000 claims description 3
- 229950011008 tetrachloroethylene Drugs 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 238000005516 engineering process Methods 0.000 claims description 2
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical group [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 claims 3
- 230000001804 emulsifying effect Effects 0.000 claims 1
- 238000009210 therapy by ultrasound Methods 0.000 claims 1
- 206010067171 Regurgitation Diseases 0.000 abstract description 17
- 238000001514 detection method Methods 0.000 abstract description 11
- 206010036790 Productive cough Diseases 0.000 abstract description 10
- 208000024794 sputum Diseases 0.000 abstract description 10
- 210000003802 sputum Anatomy 0.000 abstract description 10
- 206010011224 Cough Diseases 0.000 abstract description 6
- 230000000694 effects Effects 0.000 description 12
- 239000004005 microsphere Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 210000004051 gastric juice Anatomy 0.000 description 11
- 231100000331 toxic Toxicity 0.000 description 10
- 230000002588 toxic effect Effects 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 210000003238 esophagus Anatomy 0.000 description 6
- 238000007789 sealing Methods 0.000 description 6
- 102000057297 Pepsin A Human genes 0.000 description 5
- 108090000284 Pepsin A Proteins 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 210000004400 mucous membrane Anatomy 0.000 description 5
- 229940111202 pepsin Drugs 0.000 description 5
- 210000003296 saliva Anatomy 0.000 description 5
- 210000003437 trachea Anatomy 0.000 description 5
- 206010062717 Increased upper airway secretion Diseases 0.000 description 4
- 239000011162 core material Substances 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 210000003800 pharynx Anatomy 0.000 description 4
- 208000026435 phlegm Diseases 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000033386 Buerger disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 201000009053 Neurodermatitis Diseases 0.000 description 2
- 208000033809 Suppuration Diseases 0.000 description 2
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000000729 antidote Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 239000003535 biological staining Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 208000029039 cyanide poisoning Diseases 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 238000009775 high-speed stirring Methods 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 210000000867 larynx Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 208000005135 methemoglobinemia Diseases 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000004753 textile Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 201000008197 Laryngitis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010044302 Tracheitis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000000959 ear middle Anatomy 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/006—Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Plasma & Fusion (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Optics & Photonics (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The application discloses a preparation method of a color developing oral capsule for detecting laryngopharynx reflux disease, which comprises the following steps: coating the non-degradable polymer material on the outer side of the color developing agent to form color developing particles; and filling the color developing particles into a hollow capsule body to obtain the color developing oral capsule. The chromogenic oral capsule prepared by the application is low in cost and suitable for being generally used clinically, and a patient can judge whether laryngopharynx regurgitation exists or not by observing the color change of sputum spitted out by cough, so that the chromogenic oral capsule can truly become an objective, accurate, simple, convenient, cheap and safe laryngopharynx regurgitation detection mode, and has great economic value and social significance.
Description
Technical Field
The invention relates to the field of medicines and medical instruments, in particular to a preparation method of a color developing oral capsule for detecting laryngopharynx reflux diseases.
Background
Laryngopharyngeal reflux disease is a series of syndromes caused by the reflux of gastric contents to laryngeal cavities, trachea, lung, pharyngeal cavity, nasal cavity, oral cavity, middle ear and other parts, and various syndromes occur due to the erosion of gastric juice on mucous membranes of upper and lower airways. Such as chronic pharyngitis, rhinitis, otitis media, laryngitis, tracheitis, asthma, throat tumors, etc. The morbidity is very high, and the initial estimation of the morbidity of the population is 5-10%.
At present, the clinical diagnosis of laryngopharyngeal reflux is mainly based on subjective speculation of symptom sign scores and experimental acid-resistant treatment, and accurate diagnosis is difficult. The objective detection method mainly comprises 24-hour esophagus pH value detection, saliva pepsin detection and the like. The gastric juice contains high-concentration hydrochloric acid and specific pepsin, the gastric juice flows back to the laryngopharynx part through the esophagus, so that the pH value of the esophagus and the laryngopharynx part is reduced, the pepsin in the saliva mainly comes from the gastric juice, and whether the gastric juice flows back can be judged by detecting the pH value of the esophagus and the content of the pepsin. The detection of the PH value of the esophagus is a current clinical standard detection mode, but the cost is high, one PH value detector is nearly 100 thousands, only 1 person can be detected in one day, the method is to insert a detection catheter into the laryngeal part of the pharynx and the esophagus from the nasal cavity to detect the PH value, the pain of a patient is great, and laryngopharyngeal regurgitation is often expressed as sometimes or not, the regurgitation does not happen when the patient is detected, and the inspection is not performed in turn when the regurgitation exists, so the positive rate is low, and the clinical practicability is influenced; 3000-element saliva pepsin is used for 1 person, the specificity and the sensitivity are not high at present, and no reflux condition exists during detection, so that the detection is rarely developed clinically.
Therefore, finding an objective, accurate, simple, cheap and safe laryngopharyngeal reflux detection method is a problem which needs to be solved urgently in clinic.
Disclosure of Invention
The invention provides a preparation method of a color developing oral capsule for detecting laryngopharynx reflux disease aiming at the problems.
The technical scheme adopted by the invention is as follows:
a preparation method of a color developing oral capsule for detecting laryngopharynx reflux disease comprises the following steps:
coating the transparent non-degradable polymer material on the outer side of the color developing agent to form color developing particles;
and filling the color developing particles into a hollow capsule body to obtain the color developing oral capsule.
The key node based on the production of laryngopharynx regurgitation series disease is that gastric juice has flowed back to positions such as laryngopharynx, trachea from the stomach, the theory of operation of the color development oral capsule of this application: can conveniently swallow through the capsule body, and avoid the color development granule to pollute laryngopharynx portion, after the oral capsule of color development got into the stomach, the capsule body dissolved, released the color development microballon, the color development microballon disperses into gastric juice, if there is the laryngopharynx palirrhea, the color development agent in the gastric juice probably dyes mucous membrane, phlegm saliva secretion at laryngopharynx position, and whether the patient observes the color change of the phlegm of coughing and spitting out and can judge that there is the laryngopharynx to flow backwards. The transparent layer is a non-degradable high polymer material, can safely coat the color developing agent, and the color developing microspheres are not degraded and absorbed, so that the color developing result is accurate and objective, safe and free from toxic and side effects.
By adopting an oral administration mode, whether laryngopharynx regurgitation exists can be judged by observing the color of the sputum spitted by cough, and the method is simple and convenient and is painless; the developing microsphere capsule can be taken for several days and several weeks, so that missed diagnosis is reduced; the developing microspheres are not degraded and absorbed, the developing result is accurate and objective, and the developing microspheres are safe and have no toxic or side effect; the preparation cost is low, and the preparation method is suitable for clinical common use. The method can really become an objective, accurate, simple, convenient, cheap and safe method for detecting laryngopharyngeal reflux, and has great economic value and social significance.
In practical use, the application method comprises the following steps: the patient suspected of laryngopharynx regurgitation takes the chromogenic microsphere capsule by himself/herself, 1-2 granules are taken each time, 1-4 times a day, sputum chromogenic is stopped to take the medicine, and the medicine is determined to be laryngopharynx regurgitation positive; the oral administration for 7-14 days has no color development and no medicine stopping, and is determined as negative laryngopharyngeal reflux.
In one embodiment of the present invention, the color-developing particles are in the micron or nanometer size and are prepared by microencapsulation. The color developing particles are in micro-scale or nano-scale, so that the color developing particles do not influence the color development and cause complications of gastrointestinal stimulation and gastrointestinal absorption.
In one embodiment of the present invention, the color-developing particles are prepared by a phase separation method, a physical mechanical method or an interfacial polymerization method.
In one embodiment of the present invention, the non-degradable polymer material is polyamide, silicone rubber, polyvinyl acid resin or polyvinyl alcohol.
The capsule body of the application can be any capsule body which can be dissolved in the stomach. In one embodiment of the present invention, the capsule body is a gelatin capsule body.
In one embodiment of the present invention, the color developer is a natural dye or a synthetic dye.
In one embodiment of the present invention, the color-developing agent is methylene blue.
In one embodiment of the present invention, the color-developing particles are prepared by interfacial polymerization, and the preparation process includes:
(1) preparing a water phase: adding polyvinyl alcohol (protective colloid) and OP-10 (emulsifier) into distilled water to form a mixed solution of 3.0 mass percent of polyvinyl alcohol and 1.5 mass percent of OP-10, uniformly stirring by using a magnetic stirrer, and adjusting the pH value to 12-13 by using 25 percent of NaOH solution to obtain the water phase.
(2) Preparing an organic phase: dissolving methylene blue (core material) and paraphthaloyl chloride (wall material) in tetrachloroethylene to form a mixed solution with the molar ratio of the core to the wall being 1:5, and uniformly dispersing the mixed solution by using ultrasonic with the power of 800W to prepare an organic phase.
(3) Emulsification: the organic phase was added to the aqueous phase (volume ratio 15:85) with high speed stirring and emulsified for 20min with stirring.
(4) Encapsulation: adding an ethylene diamine aqueous solution into a constant-pressure dropping funnel at a reaction temperature of 25 ℃ within 5min at a constant speed, wherein the molar ratio of the ethylene diamine to the terephthaloyl chloride is 2:1, reacting for 15min, and finally filtering and washing to obtain the polyamide-coated methylene blue color developing particles (the average particle size is 7.1 mu m).
The polyamide is a high polymer containing amide groups in a main chain repeating unit of a macromolecule, is a transparent high polymer material with high strength, stability to acid and alkali, no absorption, no degradation and no toxic or side effect, and is a main component for manufacturing surgical operation sutures. The textile industry is often used to make microcapsule materials for coating dyes, improving the level-dyeing property and the color fixation property of the dyes. The polyamide is used as a capsule material to wrap the color developing agent to form color developing particles, and has the advantages of excellent color development, good sealing property, no degradation, no absorption and no toxic or side effect.
Methylene blue is dark blue, and the sputum can turn blue with a very small amount of methylene blue, the contrast is bright, and no blue substance is generated in laryngopharynx, trachea and lung; other colors may affect the observation results due to bleeding (red), exudation (yellow, orange), necrotic suppuration (green, black), etc.; methylene blue is used as a biological staining agent and is clinically used for identifying benign and malignant lesions of nasal pharynx and larynx, gastrointestinal tract and tracheal mucosa; the traditional Chinese medicine composition is clinically used as an antidote for treating methemoglobinemia and cyanide poisoning, and is also used for treating thromboangiitis obliterans, neurodermatitis, lithangiuria (oral administration) and the like. However, oral pure methylene blue has obvious stimulation to gastrointestinal tracts, is commonly suffered from side effects of nausea, vomiting, diarrhea and the like, and can induce or aggravate laryngopharyngeal reflux; and after being absorbed by the stomach and intestine, the methylene blue possibly secretes polluted sputum from mucous membranes such as laryngopharynx and the like, so that the judgment of results is influenced. Methylene blue is a safer drug, but a few also cause headache, blood pressure decrease, arrhythmia, and even disturbance of consciousness. Urine is blue, and urination prick pain is a common symptom. Therefore, oral administration of methylene blue as a color developing agent for laryngopharynx regurgitation still needs to be subjected to sealing and isolating treatment, and the methylene blue (the color developing agent) is wrapped by a transparent layer made of a non-degradable polymer material to form methylene blue microspheres (color developing particles), so that the oral administration of methylene blue has the advantages of excellent color development, good sealing property, no degradation, no absorption and no toxic or side effect.
The invention has the beneficial effects that: the chromogenic oral capsule prepared by the application is low in cost and suitable for being generally used clinically, and a patient can judge whether laryngopharynx regurgitation exists or not by observing the color change of sputum spitted out by cough, so that the chromogenic oral capsule can truly become an objective, accurate, simple, convenient, cheap and safe laryngopharynx regurgitation detection mode, and has great economic value and social significance.
Description of the drawings:
FIG. 1 is a schematic representation of a chromogenic oral capsule made by the process of the present application;
FIG. 2 is a cross-sectional view of a chromogenic oral capsule made by the method of the present application.
The figures are numbered:
1. a capsule body; 2. a color developing particle; 3. a color-developing agent; 4. non-degradable high molecular material.
The specific implementation mode is as follows:
the present invention will be described in detail below with reference to the accompanying drawings.
As shown in fig. 1 and 2, a method for preparing a chromogenic oral capsule for detecting laryngopharyngeal reflux disease comprises the following steps:
coating the transparent non-degradable polymer material 4 on the outer side of the color developing agent 3 to form color developing particles 2;
and filling the color developing particles 2 into the hollow capsule body 1 to obtain the color developing oral capsule.
The key node based on the production of laryngopharynx regurgitation series disease is that gastric juice has flowed back to positions such as laryngopharynx, trachea from the stomach, the theory of operation of the color development oral capsule of this application: can conveniently swallow through the capsule body, and avoid the color development granule to pollute laryngopharynx portion, after the oral capsule of color development got into the stomach, the capsule body dissolved, released the color development microballon, the color development microballon disperses into gastric juice, if there is the laryngopharynx palirrhea, the color development agent in the gastric juice probably dyes mucous membrane, phlegm saliva secretion at laryngopharynx position, and whether the patient observes the color change of the phlegm of coughing and spitting out and can judge that there is the laryngopharynx to flow backwards. The transparent layer is a non-degradable high polymer material, can safely coat the color developing agent, and the color developing microspheres are not degraded and absorbed, so that the color developing result is accurate and objective, safe and free from toxic and side effects.
By adopting an oral administration mode, whether laryngopharynx regurgitation exists can be judged by observing the color of the sputum spitted by cough, and the method is simple and convenient and is painless; the developing microsphere capsule can be taken for several days and several weeks, so that missed diagnosis is reduced; the developing microspheres are not degraded and absorbed, the developing result is accurate and objective, and the developing microspheres are safe and have no toxic or side effect; the preparation cost is low, and the preparation method is suitable for clinical common use. The method can really become an objective, accurate, simple, convenient, cheap and safe method for detecting laryngopharyngeal reflux, and has great economic value and social significance.
In practical use, the application method comprises the following steps: the patient suspected of laryngopharynx regurgitation takes the chromogenic microsphere capsule by himself/herself, 1-2 granules are taken each time, 1-4 times a day, sputum chromogenic is stopped to take the medicine, and the medicine is determined to be laryngopharynx regurgitation positive; the oral administration for 7-14 days has no color development and no medicine stopping, and is determined as negative laryngopharyngeal reflux.
In practical application, the color-developing particles 2 are micron-sized or nano-sized and are prepared by microencapsulation technology. The color developing particles are in micro-scale or nano-scale, so that the color developing particles do not influence the color development and cause complications of gastrointestinal stimulation and gastrointestinal absorption.
In practice, the microencapsulation technique can be carried out by various conventional methods such as a phase separation method, a physical mechanical method, and an interfacial polymerization method.
In this embodiment, the non-degradable polymer material 4 is polyamide, silicone rubber, polyvinyl acid resin or polyvinyl alcohol.
The capsule body of the application can be any capsule body which can be dissolved in the stomach. In one embodiment of the present invention, the capsule body is a gelatin capsule body.
In actual use, the color developing agent can be natural dye or synthetic dye. In this embodiment, the color-developing agent is methylene blue.
In one embodiment of the present invention, the color-developing particles are prepared by interfacial polymerization, and the preparation process includes:
(1) preparing a water phase: adding polyvinyl alcohol (protective colloid) and OP-10 (emulsifier) into distilled water to form a mixed solution of 3.0 mass percent of polyvinyl alcohol and 1.5 mass percent of OP-10, uniformly stirring by using a magnetic stirrer, and adjusting the pH value to 12-13 by using 25 percent of NaOH solution to obtain the water phase.
(2) Preparing an organic phase: dissolving methylene blue (core material) and paraphthaloyl chloride (wall material) in tetrachloroethylene to form a mixed solution with the molar ratio of the core to the wall being 1:5, and uniformly dispersing the mixed solution by using ultrasonic with the power of 800W to prepare an organic phase.
(3) Emulsification: the organic phase was added to the aqueous phase (volume ratio 15:85) with high speed stirring and emulsified for 20min with stirring.
(4) Encapsulation: adding an ethylene diamine aqueous solution into a constant-pressure dropping funnel at a reaction temperature of 25 ℃ within 5min at a constant speed, wherein the molar ratio of the ethylene diamine to the terephthaloyl chloride is 2:1, reacting for 15min, and finally filtering and washing to obtain the polyamide-coated methylene blue color developing particles (the average particle size is 7.1 mu m).
The polyamide is a high polymer containing amide groups in a main chain repeating unit of a macromolecule, is a transparent high polymer material with high strength, stability to acid and alkali, no absorption, no degradation and no toxic or side effect, and is a main component for manufacturing surgical operation sutures. The textile industry is often used to make microcapsule materials for coating dyes, improving the level-dyeing property and the color fixation property of the dyes. The polyamide is used as a capsule material to wrap the color developing agent to form color developing particles, and has the advantages of excellent color development, good sealing property, no degradation, no absorption and no toxic or side effect.
Methylene blue is dark blue, and the sputum can turn blue with a very small amount of methylene blue, the contrast is bright, and no blue substance is generated in laryngopharynx, trachea and lung; other colors may affect the observation results due to bleeding (red), exudation (yellow, orange), necrotic suppuration (green, black), etc.; methylene blue is used as a biological staining agent and is clinically used for identifying benign and malignant lesions of nasal pharynx and larynx, gastrointestinal tract and tracheal mucosa; the traditional Chinese medicine composition is clinically used as an antidote for treating methemoglobinemia and cyanide poisoning, and is also used for treating thromboangiitis obliterans, neurodermatitis, lithangiuria (oral administration) and the like. However, oral pure methylene blue has obvious stimulation to gastrointestinal tracts, is commonly suffered from side effects of nausea, vomiting, diarrhea and the like, and can induce or aggravate laryngopharyngeal reflux; and after being absorbed by the stomach and intestine, the methylene blue possibly secretes polluted sputum from mucous membranes such as laryngopharynx and the like, so that the judgment of results is influenced. Methylene blue is a safer drug, but a few also cause headache, blood pressure decrease, arrhythmia, and even disturbance of consciousness. Urine is blue, and urination prick pain is a common symptom. Therefore, oral administration of methylene blue as a color developing agent for laryngopharynx regurgitation still needs to be subjected to sealing and isolating treatment, and the methylene blue (the color developing agent) is wrapped by a transparent layer made of a non-degradable polymer material to form methylene blue microspheres (color developing particles), so that the oral administration of methylene blue has the advantages of excellent color development, good sealing property, no degradation, no absorption and no toxic or side effect.
The above description is only for the preferred embodiment of the present invention and is not intended to limit the scope of the present invention, and all equivalent structural changes made by using the contents of the present specification and the drawings can be directly or indirectly applied to other related technical fields and are included in the scope of the present invention.
Claims (8)
1. A preparation method of a color developing oral capsule for detecting laryngopharynx reflux disease is characterized by comprising the following steps:
coating the transparent non-degradable high polymer material on the outer side of the color developing agent by a microencapsulation technology to form color developing particles;
and filling the color developing particles into a hollow capsule body to obtain the color developing oral capsule.
2. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease according to claim 1, wherein the chromogenic particles are in the micro-scale or nano-scale.
3. The method for preparing a chromogenic oral capsule for detecting laryngopharyngeal reflux disease according to claim 2, wherein the chromogenic particles are prepared by a phase separation method, a physical mechanical method or an interfacial polymerization method.
4. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease according to claim 1, wherein the non-degradable polymer material is polyamide, silicone rubber, polyvinyl acid resin or polyvinyl alcohol.
5. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease according to claim 1, wherein the capsule body is a gelatin capsule body.
6. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease as claimed in claim 1, wherein the chromogenic agent is a natural dye or a synthetic dye.
7. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease as claimed in claim 6, wherein the chromogenic agent is methylene blue.
8. The method for preparing the chromogenic oral capsule for detecting laryngopharyngeal reflux disease according to claim 7, wherein the chromogenic particles are prepared by interfacial polymerization, and the preparation process comprises:
(1) preparing a water phase: adding polyvinyl alcohol and OP-10 into distilled water to form a mixed solution of the polyvinyl alcohol with the mass fraction of 3.0% and the OP-10 with the mass fraction of 1.5%, uniformly stirring, and adjusting the pH value to 12-13 by using a 25% NaOH solution to prepare a water phase;
(2) preparing an organic phase: dissolving methylene blue and terephthaloyl chloride in tetrachloroethylene, wherein the molar ratio of the methylene blue to the terephthaloyl chloride is 1:5, and uniformly dispersing all the components by ultrasonic treatment to obtain an organic phase;
(3) emulsification: adding the organic phase into the water phase, wherein the volume ratio of the organic phase to the water phase is 15:85, and stirring and emulsifying for 20 min;
(4) encapsulation: and (2) adding an ethylene diamine aqueous solution into a constant-pressure dropping funnel at a reaction temperature of 25 ℃ within 5min at a constant speed, wherein the molar ratio of ethylene diamine to terephthaloyl chloride is 2:1, reacting for 15min, and finally filtering and washing to obtain the polyamide-coated methylene blue color developing particles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110492173.XA CN113209314A (en) | 2021-05-06 | 2021-05-06 | Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110492173.XA CN113209314A (en) | 2021-05-06 | 2021-05-06 | Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113209314A true CN113209314A (en) | 2021-08-06 |
Family
ID=77091229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110492173.XA Pending CN113209314A (en) | 2021-05-06 | 2021-05-06 | Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113209314A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1471429A (en) * | 2000-11-06 | 2004-01-28 | �Ϻ���ͨ��ѧ | Core-shell particles and process of theie preparation |
| CN106622054A (en) * | 2016-12-19 | 2017-05-10 | 天津大学 | Method for preparing polyamide double-layer microcapsule |
| WO2020127749A1 (en) * | 2018-12-19 | 2020-06-25 | Firmenich Sa | Process for preparing polyamide microcapsules |
-
2021
- 2021-05-06 CN CN202110492173.XA patent/CN113209314A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1471429A (en) * | 2000-11-06 | 2004-01-28 | �Ϻ���ͨ��ѧ | Core-shell particles and process of theie preparation |
| CN106622054A (en) * | 2016-12-19 | 2017-05-10 | 天津大学 | Method for preparing polyamide double-layer microcapsule |
| WO2020127749A1 (en) * | 2018-12-19 | 2020-06-25 | Firmenich Sa | Process for preparing polyamide microcapsules |
Non-Patent Citations (5)
| Title |
|---|
| 尤新民等: "《围术期气道管理》", 31 August 2010, 上海世界图书出版公司 * |
| 李川等: "缓释技术及其在食品工业中的应用", 《食品与机械》 * |
| 栾强等: "《精编耳鼻喉疾病临床诊疗》", 30 June 2018, 上海交通大学出版社 * |
| 王飞利等: "聚酰胺微胶囊分散染料的制备及其缓释性能", 《应用化学》 * |
| 绀户朝治: "《微胶囊工艺学》", 31 December 1989, 轻工业出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Nseir et al. | Microaspiration in intubated critically ill patients: diagnosis and prevention | |
| Thompson-Henry et al. | The modified Evan's blue dye procedure fails to detect aspiration in the tracheostomized patient: five case reports | |
| CN107714642A (en) | A kind of oral solution of EV71 viruses and CVA16 viral inhibitors and preparation method thereof | |
| CN108478785A (en) | A kind of oral insulin micelle nano grain and preparation method thereof | |
| CN113209314A (en) | Preparation method of color developing oral capsule for detecting laryngopharyngeal reflux disease | |
| Abdi et al. | pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions | |
| CN116898873A (en) | Polyethylene glycol compound combination medicine and preparation method thereof | |
| US6447763B1 (en) | Method and system for production and collection of lavage induced stool (LIS) for chemical and biologic tests of cells | |
| CN105025879B (en) | Identification release includes nanoporous base material, their preparation method and the purposes of activating agent | |
| Zhu et al. | Contrast‐Enhanced Ultrasound Diagnosed a Pyriform Sinus Fistula That Failed to Be Diagnosed by a Barium Swallow Examination: Case Report and Review of Choices for the Imaging Examination. | |
| Cobaugh et al. | Cocaine balloon aspiration: successful removal with bronchoscopy | |
| CN115531411A (en) | Medicine with dual functions of CT imaging and treatment and preparation method and application thereof | |
| CN113116818B (en) | Encapsulated bodies and their use for producing medicaments or foodstuffs | |
| CN113116863B (en) | Percutaneous absorption patch and application and preparation method thereof | |
| CN109224083B (en) | Application of poloxamer-modified iron oxide nanoparticles in preparation of drugs for treating non-alcoholic fatty liver diseases | |
| CN116869927B (en) | Esophageal thermosensitive gel for treating eosinophilic esophagitis | |
| CN110522739A (en) | A kind of difunctional load insulin mixed micelle nanoparticle of pH sensitivity/film adhesiveness and preparation method thereof | |
| CA2291685C (en) | Pharmaceutical product for the detection of helicobacter pylori-induced gastrointestinal disorder | |
| EP1575620B1 (en) | Bio-degradable microspheres for diagnosing gastroesophagal reflux | |
| Pathak et al. | Superiority of non-capsulated 14C-urea breath test over capsule based method for detection of Helicobacter pylori infection–a preliminary report | |
| Singh et al. | Carotenaemia in Alzheimer's disease. | |
| CN108379225A (en) | Amphipathic oral medicament-carried nano micelle of one kind and preparation method thereof | |
| Singh et al. | Esophageal foreign body in a neonate: an unusual age of presentation | |
| CN221357782U (en) | Nasal feeding tube for early warning gastric reflux | |
| CN106699925A (en) | Acid-soluble chitosan bismuth and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210806 |