CN108542897A - A kind of application for treating canker sore - Google Patents
A kind of application for treating canker sore Download PDFInfo
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- CN108542897A CN108542897A CN201810497352.0A CN201810497352A CN108542897A CN 108542897 A CN108542897 A CN 108542897A CN 201810497352 A CN201810497352 A CN 201810497352A CN 108542897 A CN108542897 A CN 108542897A
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- Prior art keywords
- temperature sensitive
- application
- collagen
- film
- gel
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- 208000020670 canker sore Diseases 0.000 title claims abstract description 39
- 102000008186 Collagen Human genes 0.000 claims abstract description 73
- 108010035532 Collagen Proteins 0.000 claims abstract description 73
- 229920001436 collagen Polymers 0.000 claims abstract description 73
- 239000002131 composite material Substances 0.000 claims abstract description 46
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 28
- 230000001741 anti-phlogistic effect Effects 0.000 claims abstract description 28
- 230000003115 biocidal effect Effects 0.000 claims abstract description 27
- 229920000742 Cotton Polymers 0.000 claims abstract description 24
- 239000003292 glue Substances 0.000 claims abstract description 19
- 239000012528 membrane Substances 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000003937 drug carrier Substances 0.000 claims abstract description 15
- 238000002955 isolation Methods 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 32
- 239000000835 fiber Substances 0.000 claims description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 17
- 230000033444 hydroxylation Effects 0.000 claims description 11
- 238000005805 hydroxylation reaction Methods 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 210000002435 tendon Anatomy 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- -1 polyethylene Polymers 0.000 claims description 8
- 102000012422 Collagen Type I Human genes 0.000 claims description 7
- 108010022452 Collagen Type I Proteins 0.000 claims description 7
- 239000004698 Polyethylene Substances 0.000 claims description 7
- 229920000573 polyethylene Polymers 0.000 claims description 7
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 claims description 5
- 239000007983 Tris buffer Substances 0.000 claims description 5
- SGRYPYWGNKJSDL-UHFFFAOYSA-N amlexanox Chemical compound NC1=C(C(O)=O)C=C2C(=O)C3=CC(C(C)C)=CC=C3OC2=N1 SGRYPYWGNKJSDL-UHFFFAOYSA-N 0.000 claims description 5
- 229960003731 amlexanox Drugs 0.000 claims description 5
- 239000007853 buffer solution Substances 0.000 claims description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 5
- 230000008595 infiltration Effects 0.000 claims description 5
- 238000001764 infiltration Methods 0.000 claims description 5
- 229940044519 poloxamer 188 Drugs 0.000 claims description 5
- 229920001993 poloxamer 188 Polymers 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- ILXAOQAXSHVHTM-UHFFFAOYSA-M sodium;2-amino-2-(hydroxymethyl)propane-1,3-diol;chloride Chemical compound [Na+].[Cl-].OCC(N)(CO)CO ILXAOQAXSHVHTM-UHFFFAOYSA-M 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 4
- 241000283074 Equus asinus Species 0.000 claims description 4
- 239000004098 Tetracycline Substances 0.000 claims description 4
- 229930003270 Vitamin B Natural products 0.000 claims description 4
- 229930003268 Vitamin C Natural products 0.000 claims description 4
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 claims description 4
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims description 4
- 229960001180 norfloxacin Drugs 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 229960002180 tetracycline Drugs 0.000 claims description 4
- 229930101283 tetracycline Natural products 0.000 claims description 4
- 235000019364 tetracycline Nutrition 0.000 claims description 4
- 150000003522 tetracyclines Chemical class 0.000 claims description 4
- 235000019156 vitamin B Nutrition 0.000 claims description 4
- 239000011720 vitamin B Substances 0.000 claims description 4
- 235000019154 vitamin C Nutrition 0.000 claims description 4
- 239000011718 vitamin C Substances 0.000 claims description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- 229920001971 elastomer Polymers 0.000 claims description 3
- 239000010248 fenbid Substances 0.000 claims description 3
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 3
- 229960001763 zinc sulfate Drugs 0.000 claims description 3
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 2
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
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- 235000015278 beef Nutrition 0.000 claims description 2
- 229940116229 borneol Drugs 0.000 claims description 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 claims description 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 claims description 2
- 239000012557 regeneration buffer Substances 0.000 claims description 2
- 239000009306 yunnan baiyao Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 12
- 210000000214 mouth Anatomy 0.000 abstract description 12
- 241000283984 Rodentia Species 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 229920002545 silicone oil Polymers 0.000 abstract description 4
- 230000029663 wound healing Effects 0.000 abstract description 4
- 230000036760 body temperature Effects 0.000 abstract description 3
- 230000037314 wound repair Effects 0.000 abstract description 2
- 238000012827 research and development Methods 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 40
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- 239000004814 polyurethane Substances 0.000 description 14
- 229920002635 polyurethane Polymers 0.000 description 13
- 208000025865 Ulcer Diseases 0.000 description 11
- 231100000397 ulcer Toxicity 0.000 description 10
- 239000000872 buffer Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
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- 208000002399 aphthous stomatitis Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
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- 210000004700 fetal blood Anatomy 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
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- 238000012986 modification Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 2
- 206010006326 Breath odour Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 208000032139 Halitosis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010029803 Nosocomial infection Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001637 borneol derivatives Chemical class 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 208000022532 enlargement of lymph nodes Diseases 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
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- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
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- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
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- 210000003296 saliva Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
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- 210000001584 soft palate Anatomy 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
Classifications
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- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- Animal Behavior & Ethology (AREA)
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- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Natural Medicines & Medicinal Plants (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of applications for treating canker sore, it is applied including temperature sensitive type collagen base composite antibiotic antiphlogistic gel and pharmaceutical carrier, the pharmaceutical carrier application includes PU composite membranes, medical waterproof pressure sensitive glue, absorbent cotton thin slice, the release paper (film) for being coated with silicone oil antitack agent.The application that the present invention treats canker sore makes full use of to solidify not trickle under the body temperature that the medical new material of temperature sensitive type collagen-based gel has and characteristic and can be merged with musculature and good wound repair function, research and development are very suitable for the application product of the closing isolation of the oral cavity open sore part, the open sore part can not only be kept to clean, friction when reducing laboratory rodent chow to the open sore part, and it can also be directly as pharmaceutical carrier, so that drug is persistently bonded the open sore part, in favor of playing curative effect of medication, promotes wound healing.
Description
Technical field
The present invention relates to canker sore prevention and control fields, relate in particular to a kind of application for treating canker sore.
Background technology
Canker sore is commonly called as " aphtha ", is a kind of common ulcerative damages illness for betiding mucous membrane of mouth, is more common in
Expose the group of following sensitivity since oral mucosa ruptures in the positions such as lip inside, tongue, tongue abdomen, cheek mucous membrane, vestibular ditch, soft palate
It knits, so sharp ache when ulcer is broken out, local cusalgia is apparent, when especially having a meal or touching irritable food, pain meeting
More acutely, unbearably, the aphtha of weight extends to whole oral cavity to cusalgia.
Canker sore is not effectively treated, and morbidity shows as canker sore breaking-out increasingly in gradually aggravation trend
Frequently, ulcer surface is more and more, and ulcer breaking-out duration extends, or even develops to the situation continued not more.Canker sore
Diet can also be influenced, spoken, very big inconvenience is caused to daily life；Can concurrent halitosis, chronic pharyngitis, constipation, headache, dizziness,
The constitutional symptoms such as nauseous, weak, irritated, fever, enlargement of lymph nodes are serious even to cause canceration.
Invention content
Technical problem to be solved by the invention is to provide the applications that a kind of curative effect reliably treats canker sore.
In order to solve the above-mentioned technical problem, the present invention adopts the following technical scheme that：A kind of application for treating canker sore, packet
Temperature sensitive type collagen base composite antibiotic antiphlogistic gel and pharmaceutical carrier application are included, the pharmaceutical carrier application includes PU composite membranes, doctor
Preparation method with waterproof pressure sensitive glue, absorbent cotton thin slice, release paper (film), the application of the treatment canker sore includes following step
Suddenly：
(1) medical waterproof pressure sensitive glue is coated on PU composite membranes；
(2) the first release paper (film) in a ring is sticked on the PU composite membranes periphery for having applied medical waterproof pressure sensitive glue；
(3) the centre one layer of absorbent cotton of stickup for not pasting the first release paper (film) on PU composite membranes described above is thin
Piece；
It (4) will be in infiltration to absorbent cotton thin slice under temperature sensitive type collagen base composite antibiotic antiphlogistic gel low temperature；
(5) second is covered on the absorbent cotton thin slice for being impregnated with temperature sensitive type collagen base composite antibiotic antiphlogistic gel at normal temperatures
Release paper (film), be covered each by last first release paper (film) described above and the second release paper (film) polyethylene network every
From film.
Further, the temperature sensitive type collagen base composite antibiotic antiphlogistic gel is prepared as follows：
(1) it is hydroxylated the preparation of regenerated collagen fiber solution
The Type I collagen of 1~5 parts by weight is taken, the 10mM hydrochloric acid for being dissolved in 100~500 parts by volume is stirred at 4~10 DEG C
In solution, after collagen is completely dissolved, it is slowly added to hydrochloric acid solution equal volume containing 30~50mM Tris, 0.1~
The Tris-NaCl buffer solutions that the pH value of 0.2M NaCl composition is 8.0 stir at 4~10 DEG C, regeneration collagen are made
Fiber buffer stoste；Then above-mentioned regeneration Buffer stock is statically placed in 25~37 DEG C of constant incubator, cultivates 0.5~5h,
Regenerated collagen fiber solution is made；A concentration of 50U/g~150U/g glutamine transaminages are finally added to above-mentioned reclaimed rubber
In fibrinogen solution, it is sufficiently stirred 10 at 4~10 DEG C~for 24 hours, hydroxylation regenerated collagen fiber solution is prepared；
(2) preparation of temperature sensitive type collagen-based gel
The polyvinylpyrrolidone of the poloxamer188 of 0.5~5 parts by weight and 0.5~5 parts by weight is added to above-mentioned hydroxyl
Change in regenerated collagen fiber solution, is sufficiently stirred 5~12h at 4~10 DEG C, temperature sensitive type collagen-based gel is prepared；
(3) preparation of temperature sensitive type collagen base composite antibiotic antiphlogistic gel
The Aphthasol object of 0.5~2 parts by weight is added in above-mentioned temperature sensitive type collagen-based gel, at 4~10 DEG C
It is sufficiently stirred 0.5~2h.
Temperature sensitive type collagen base composite antibiotic antiphlogistic gel is waited for through gamma-rays sterilization with cleaning container package Cord blood
With；Its Key Performance Indicator is as follows：
Appearance：Gel, surface is smooth, the impurity being visible by naked eyes；
Mass fraction shared by moisture：≤ 10%；
Gel strength：100~500g/cm 2；
Content of beary metal：≤10μg/g；
Cytotoxicity：Cell-cytotoxic reaction is not more than 1 grade；
Sterility test：It is sterile；
Sensitization test (STT)：Without delayed type hypersensitivity, DTH；
Intradermal reaction is tested：Primary stimulus index PII<0.4；
Gel time：5~20s.
Further, the Type I collagen is from pigskin, pig tendon, ox-hide, beef tendon, donkey hide, donkey tendon, horse skin, horse tendon, mouse
What any one of skin or rat-tail tendon prepared.
Further, the hydroxylation regenerated collagen fiber is the regenerated collagen fiber of 30~65% proline hydroxylation.
Further, the Aphthasol object is vitamin B compound, vitamin C, tannalbin, zinc sulfate, cloud
At least one of southern baiyao, borneol, Ying Taiqing, Fenbid, Voltarol, Norfloxacin ointment, tetracycline (ratio is unlimited).
The application application method that the present invention treats canker sore is as follows：
The open sore part is cleaned, open sore part periphery moisture is blotted with disinfection cotton paper, by polyethylene (PE) net in the application of Cord blood
Network isolation film and release paper (film) are torn, and the absorbent cotton thin slice for being impregnated with drug and temperature sensitive hydrogel are directed at the open sore part, application
It is covered in the open sore part, first presses polyurethane (PU) composite membrane along application periphery, make medical waterproof pressure sensitive gluing patch open sore part week flaw-piece
On skin, is then pressed lightly on again with finger alignment absorbent cotton flap position, make medicine and temperature sensitive hydrogel mixed liquor abundant
Stretch into the open sore part.
Inventor studies the reason of finding canker sore obstinate：
Since oral cavity easily invades various bacteriums and cross-infection, laboratory rodent chow usually rubs the open sore part in addition, influences the open sore part and is cured
It closes, the conventional medicine for oral administration arrival oral cavity inner membrance efficacy of a drug is small, effect is poor, so existing treatment canker sore is mostly to use externally-applied liniment,
But it smears drug in the oral cavity easily to be fallen off by saliva dissolving, these are all the cureless basic reasons of canker sore.
So to improve therapeutic effect, it is necessary to find a kind of open sore part waterproof application new material, it is de- to break through the easy dissolving of drug
The problem fallen realizes that the open sore part effectively closes isolation, keeps open sore part sanitation and hygiene, and when laboratory rodent chow avoids the open sore part that rubs, and allows treatment
Drug persists to canker sore position.
Inventor has found that the temperature sensitive type collagen-based disclosed in the Chinese invention patent application No. is 201510229099.7 is multiple
Hemostasis gel is closed, there is good blending with musculature, not only has effects that repair wound, but also with solidifying under body temperature
Gu the characteristic that do not trickle is very suitable for the closing isolation of the oral cavity open sore part, open sore part cleaning is kept, to the open sore part when reducing laboratory rodent chow
Friction, and medicament plaster can be made directly as pharmaceutical carrier, drug can be made persistently to be bonded the open sore part, in favor of playing drug
Curative effect promotes wound healing.
The present invention utilizes the good Medical special of thermo-sensitive gel new material for many problems present in dental ulcer treatment
Property, a kind of easy to use, long action time is provided, curative effect reliably treats the thermo-sensitive gel application of canker sore.
The temperature sensitive type collagen base composite antibiotic antiphlogistic gel that the present invention uses is application No. is 201510229099.7
The medical new material innovated on the basis of temperature sensitive type collagen-based compound hemostatic gel disclosed in Chinese invention patent, it not only has
Antimicrobial and anti-inflammation efficacy, and can be quickly formed for liquid when environment temperature becomes 37 DEG C or so under room temperature and low-temperature condition
Gel is very suitable for the application product of the closing isolation of the oral cavity open sore part, the open sore part can not only be kept to clean, when reducing laboratory rodent chow
Friction to the open sore part, and drug can also be made persistently to be bonded the open sore part directly as pharmaceutical carrier, in favor of playing curative effect of medication,
Promote wound healing.
Beneficial effects of the present invention are embodied in：
The application that the present invention treats canker sore makes full use of the body temperature that the medical new material of temperature sensitive type collagen-based gel has
Lower solidification is not trickled and characteristic and can merge with musculature and good wound repair function, researches and develops and is very suitable for the oral cavity open sore part
Closing isolation application product, the open sore part can not only be kept to clean, friction to open sore part when reducing laboratory rodent chow, and can also
Directly as pharmaceutical carrier, drug is made persistently to be bonded the open sore part, in favor of playing curative effect of medication, promotes wound healing.
The present invention is reliable using Aphthasol object curative effect, very high to canker sore cure rate.
Specific implementation mode
With reference to embodiment, the invention will be further described：
Various raw materials, are such as not specifically noted used in following embodiment, are commercial product well known in the art.
Embodiment 1
Treat the preparation of the application of canker sore
It is applied including temperature sensitive type collagen base composite antibiotic antiphlogistic gel and pharmaceutical carrier, the pharmaceutical carrier application is answered by PU
Close film, medical waterproof pressure sensitive glue, absorbent cotton thin slice, the compositions such as release paper (film) for being coated with silicone oil antitack agent, the treatment oral cavity
The preparation method of the application of ulcer includes the following steps：
(1) preparation of temperature sensitive type collagen base composite antibiotic antiphlogistic gel：
The Type I collagen of 3 parts by weight is taken, stirs and is dissolved in the 10mM hydrochloric acid solutions of 400 parts by volume at 7 DEG C, wait for glue
After original is completely dissolved, be slowly added to be with pH value of the hydrochloric acid solution equal volume containing 40mM Tris, 0.15M NaCl compositions
8.0 Tris-NaCl buffer solutions stir at 7 DEG C, and regenerated collagen fiber Buffer stock is made；Then by it is above-mentioned again
Raw Buffer stock is statically placed in 30 DEG C of constant incubator, cultivates 2.8h, and regenerated collagen fiber solution is made；It finally will be a concentration of
100U/g glutamine transaminages are added in above-mentioned regenerated collagen fiber solution, are sufficiently stirred 17h at 7 DEG C, hydroxyl is prepared
Change regenerated collagen fiber solution；
The polyvinylpyrrolidone of the poloxamer188 of 3 parts by weight and 3 parts by weight is added to above-mentioned hydroxylation regeneration collagen
In fiber solution, it is sufficiently stirred 9h at 7 DEG C, temperature sensitive type collagen-based gel is prepared；
By the vitamin B compound of 0.2 parts by weight, the vitamin C of 0.2 parts by weight, the zinc sulfate of 0.1 parts by weight, 0.5 weight
Part Yunnan Baiyao, the borneols of 0.1 parts by weight, 0.1 parts by weight tetracycline be added in above-mentioned temperature sensitive type collagen-based gel, 7 DEG C
Under be sufficiently stirred 1.2h, obtain temperature sensitive type collagen base composite antibiotic antiphlogistic gel；
(2) medical waterproof pressure sensitive glue is coated on PU composite membranes；
(3) the first release paper (film) in a ring is sticked on the PU composite membranes periphery for having applied medical waterproof pressure sensitive glue；
(4) the centre one layer of absorbent cotton of stickup for not pasting the first release paper (film) on PU composite membranes described above is thin
Piece；
It (5) will be in infiltration to absorbent cotton thin slice under temperature sensitive type collagen base composite antibiotic antiphlogistic gel low temperature；
(6) second is covered on the absorbent cotton thin slice for being impregnated with temperature sensitive type collagen base composite antibiotic antiphlogistic gel at normal temperatures
Release paper (film), be covered each by last first release paper (film) described above and the second release paper (film) polyethylene network every
From film.
Embodiment 2
Treat the preparation of the application of canker sore
It is applied including temperature sensitive type collagen base composite antibiotic antiphlogistic gel and pharmaceutical carrier, the pharmaceutical carrier application is answered by PU
Close film, medical waterproof pressure sensitive glue, absorbent cotton thin slice, the compositions such as release paper (film) for being coated with silicone oil antitack agent, the treatment oral cavity
The preparation method of the application of ulcer includes the following steps：
(1) preparation of temperature sensitive type collagen base composite antibiotic antiphlogistic gel：
The Type I collagen of 1 parts by weight is taken, stirs and is dissolved in the 10mM hydrochloric acid solutions of 100 parts by volume at 4 DEG C, wait for glue
After original is completely dissolved, be slowly added to be with pH value of the hydrochloric acid solution equal volume containing 30mM Tris, 0.1M NaCl compositions
8.0 Tris-NaCl buffer solutions stir at 4 DEG C, and regenerated collagen fiber Buffer stock is made；Then by it is above-mentioned again
Raw Buffer stock is statically placed in 25 DEG C of constant incubator, cultivates 0.5h, and regenerated collagen fiber solution is made；It finally will be a concentration of
50U/g glutamine transaminages are added in above-mentioned regenerated collagen fiber solution, are sufficiently stirred at 4 DEG C for 24 hours, and hydroxylation is prepared
Regenerated collagen fiber solution；
The polyvinylpyrrolidone of the poloxamer188 of 0.5 parts by weight and 0.5 parts by weight is added to above-mentioned hydroxylation regeneration
In collagenous fibres solution, it is sufficiently stirred 5h at 4 DEG C, temperature sensitive type collagen-based gel is prepared；
By the vitamin C of 0.1 parts by weight, the Ying Taiqing of 0.1 parts by weight, the Voltarol of 0.1 parts by weight, 0.2 parts by weight
Norfloxacin ointment is added in above-mentioned temperature sensitive type collagen-based gel, and 2h is sufficiently stirred at 4 DEG C, and it is compound anti-to obtain temperature sensitive type collagen-based
Bacterium antiphlogistic gel；
(2) medical waterproof pressure sensitive glue is coated on PU composite membranes；
(3) the first release paper (film) in a ring is sticked on the PU composite membranes periphery for having applied medical waterproof pressure sensitive glue；
(4) the centre one layer of absorbent cotton of stickup for not pasting the first release paper (film) on PU composite membranes described above is thin
Piece；
It (5) will be in infiltration to absorbent cotton thin slice under temperature sensitive type collagen base composite antibiotic antiphlogistic gel low temperature；
(6) second is covered on the absorbent cotton thin slice for being impregnated with temperature sensitive type collagen base composite antibiotic antiphlogistic gel at normal temperatures
Release paper (film), be covered each by last first release paper (film) described above and the second release paper (film) polyethylene network every
From film.
Embodiment 3
Treat the preparation of the application of canker sore
It is applied including temperature sensitive type collagen base composite antibiotic antiphlogistic gel and pharmaceutical carrier, the pharmaceutical carrier application is answered by PU
Close film, medical waterproof pressure sensitive glue, absorbent cotton thin slice, the compositions such as release paper (film) for being coated with silicone oil antitack agent, the treatment oral cavity
The preparation method of the application of ulcer includes the following steps：
(1) preparation of temperature sensitive type collagen base composite antibiotic antiphlogistic gel：
The Type I collagen of 5 parts by weight is taken, stirs and is dissolved in the 10mM hydrochloric acid solutions of 500 parts by volume at 10 DEG C, wait for glue
After original is completely dissolved, be slowly added to be with pH value of the hydrochloric acid solution equal volume containing 50mM Tris, 0.2M NaCl compositions
8.0 Tris-NaCl buffer solutions stir at 10 DEG C, and regenerated collagen fiber Buffer stock is made；Then by it is above-mentioned again
Raw Buffer stock is statically placed in 37 DEG C of constant incubator, cultivates 5h, and regenerated collagen fiber solution is made；It finally will be a concentration of
150U/g glutamine transaminages are added in above-mentioned regenerated collagen fiber solution, are sufficiently stirred 10h at 10 DEG C, hydroxyl is prepared
Change regenerated collagen fiber solution；
The polyvinylpyrrolidone of the poloxamer188 of 5 parts by weight and 5 parts by weight is added to above-mentioned hydroxylation regeneration collagen
In fiber solution, it is sufficiently stirred 12h at 10 DEG C, temperature sensitive type collagen-based gel is prepared；
By the vitamin B compound of 0.3 parts by weight, the tannalbin of 0.2 parts by weight, the Ying Taiqing of 0.2 parts by weight, 0.2 weight
Measure the tetracycline addition of the Fenbid of part, the Voltarol of 0.3 parts by weight, the Norfloxacin ointment of 0.2 parts by weight, 0.6 parts by weight
In above-mentioned temperature sensitive type collagen-based gel, it is sufficiently stirred 0.5h at 10 DEG C, obtains temperature sensitive type collagen base composite antibiotic antiphlogistic gel；
(2) medical waterproof pressure sensitive glue is coated on PU composite membranes；
(3) the first release paper (film) in a ring is sticked on the PU composite membranes periphery for having applied medical waterproof pressure sensitive glue；
(4) the centre one layer of absorbent cotton of stickup for not pasting the first release paper (film) on PU composite membranes described above is thin
Piece；
It (5) will be in infiltration to absorbent cotton thin slice under temperature sensitive type collagen base composite antibiotic antiphlogistic gel low temperature；
(6) second is covered on the absorbent cotton thin slice for being impregnated with temperature sensitive type collagen base composite antibiotic antiphlogistic gel at normal temperatures
Release paper (film), be covered each by last first release paper (film) described above and the second release paper (film) polyethylene network every
From film.
Embodiment 4
Treat the clinical effect trial of the application of canker sore
Selected case：Through being diagnosed as canker sore, with the one or more patient of canker sore clinical symptoms；
Usage and dosage is：As specification is recorded.
Curative effect situation criterion：1. curing.Malaise symptoms completely disappear；2. effectively.Malaise symptoms mitigate or part disappears
It loses；3. invalid.Malaise symptoms are unchanged.
Table 1 is clinical pharrnacokinetics of 300 canker sore patients using the application of the treatment canker sore of embodiment 1 to 3
Report.
1 clinical effect trial result of table
| Spray group | Number of users | Healing number | Efficiently individual quantity | Invalid number | Cure rate | Total effective rate |
| Embodiment 1 | 100 | 91 | 9 | 0 | 91% | 100% |
| Embodiment 2 | 100 | 87 | 12 | 1 | 87% | 99% |
| Embodiment 3 | 100 | 88 | 11 | 1 | 88% | 99% |
Model case is as follows：
What certain, female, 26 years old, existing many places roun ulcer on the inside of lip, concavity, surface covered yellow pseudomembrane, surrounding mucous membrane
Red and micro- swollen, cusalgia sense is strong, is diagnosed as canker sore.Two days later using the application of the invention for treating canker sore, redness is reduced,
Cusalgia sense mitigates, and after a week, recovery from illness has no any side effect, no relapse.
Chen, man, 22 years old, tongue abdomen showed many places ellipse ulcer, concavity, the white pseudomembrane of surface covering, surrounding mucous membrane
Red and micro- swollen, ulcer part cusalgia is apparent, is diagnosed as canker sore.After the application of the invention for treating canker sore three days,
Redness is reduced, and cusalgia sense mitigates, and after 10 days, recovery from illness has no any side effect, no relapse.
It should be understood that example as described herein and embodiment are not intended to restrict the invention, this field only for explanation
Technical staff can make various modifications or variation according to it, all within the spirits and principles of the present invention, made by it is any modification,
Equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (5)
1. a kind of application for treating canker sore, it is characterised in that：Including temperature sensitive type collagen base composite antibiotic antiphlogistic gel and medicine
Object carrier applies, and pharmaceutical carrier application includes PU composite membranes, medical waterproof pressure sensitive glue, absorbent cotton thin slice, release paper (film),
The preparation method of the application of the treatment canker sore includes the following steps：
(1) medical waterproof pressure sensitive glue is coated on PU composite membranes；
(2) the first release paper (film) in a ring is sticked on the PU composite membranes periphery for having applied medical waterproof pressure sensitive glue；
(3) one layer of absorbent cotton thin slice is pasted in the centre for not pasting the first release paper (film) on PU composite membranes described above；
It (4) will be in infiltration to absorbent cotton thin slice under temperature sensitive type collagen base composite antibiotic antiphlogistic gel low temperature；
(5) covering second is release on the absorbent cotton thin slice for being impregnated with temperature sensitive type collagen base composite antibiotic antiphlogistic gel at normal temperatures
Paper (film) is finally covered each by polyethylene Network Isolation in the first release paper (film) described above and the second release paper (film)
Film.
2. the application for the treatment of canker sore as described in claim 1, it is characterised in that：The temperature sensitive type collagen base composite antibiotic
Antiphlogistic gel is prepared as follows：
(1) it is hydroxylated the preparation of regenerated collagen fiber solution
The Type I collagen of 1~5 parts by weight is taken, the 10mM hydrochloric acid solutions for being dissolved in 100~500 parts by volume are stirred at 4~10 DEG C
In, after collagen is completely dissolved, it is slowly added to contain 30~50mM Tris, 0.1~0.2M with hydrochloric acid solution equal volume
The Tris-NaCl buffer solutions that the pH value of NaCl compositions is 8.0, stir at 4~10 DEG C, and it is slow that regenerated collagen fiber is made
Rush stoste；Then above-mentioned regeneration Buffer stock is statically placed in 25~37 DEG C of constant incubator, cultivates 0.5~5h, be made again
Crude rubber original fiber solution；A concentration of 50U/g~150U/g glutamine transaminages are finally added to above-mentioned regenerated collagen fiber
In solution, it is sufficiently stirred 10 at 4~10 DEG C~for 24 hours, hydroxylation regenerated collagen fiber solution is prepared；
(2) preparation of temperature sensitive type collagen-based gel
The polyvinylpyrrolidone of the poloxamer188 of 0.5~5 parts by weight and 0.5~5 parts by weight is added to above-mentioned hydroxylation again
In crude rubber original fiber solution, it is sufficiently stirred 5~12h at 4~10 DEG C, temperature sensitive type collagen-based gel is prepared；
(3) preparation of temperature sensitive type collagen base composite antibiotic antiphlogistic gel
The Aphthasol object of 0.5~2 parts by weight is added in above-mentioned temperature sensitive type collagen-based gel, at 4~10 DEG C fully
Stir 0.5~2h.
3. the application for the treatment of canker sore as claimed in claim 2, it is characterised in that：The Type I collagen is from pigskin, pig
What any one of tendon, ox-hide, beef tendon, donkey hide, donkey tendon, horse skin, horse tendon, mouse skin or rat-tail tendon prepared.
4. the application for the treatment of canker sore as claimed in claim 2, it is characterised in that：The hydroxylation regenerated collagen fiber is 30
The regenerated collagen fiber of~65% proline hydroxylation.
5. the application for the treatment of canker sore as claimed in claim 2, it is characterised in that：The Aphthasol object is multiple
Close vitamin B, vitamin C, tannalbin, zinc sulfate, Yunnan Baiyao, borneol, Ying Taiqing, Fenbid, Voltarol, Norfloxacin
At least one of ointment, tetracycline.
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| CN201810497352.0A CN108542897A (en) | 2018-05-22 | 2018-05-22 | A kind of application for treating canker sore |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810497352.0A CN108542897A (en) | 2018-05-22 | 2018-05-22 | A kind of application for treating canker sore |
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| US5972906A (en) * | 1991-07-03 | 1999-10-26 | Hyal Pharmaceutical Corporation | Treatment of mucous membrane disease, trauma or condition and for the relief of pain thereof |
| CN1522687A (en) * | 2003-02-17 | 2004-08-25 | 北京泰瑞伟业科技有限公司 | Oral health product using adhesive material as carrier |
| CN204379821U (en) * | 2014-12-25 | 2015-06-10 | 第四军医大学唐都医院 | A kind of oral ulcer film paster |
| CN204446300U (en) * | 2015-02-03 | 2015-07-08 | 广东泰宝医疗科技股份有限公司 | A kind of composite medical dressing |
| CN104888265A (en) * | 2015-05-08 | 2015-09-09 | 四川大学 | Thermosensitive collagen-based composite hemostat gel and preparation method thereof |
| CN106109445A (en) * | 2016-06-22 | 2016-11-16 | 佛山市高明绿化纳新材料有限公司 | A kind of long-acting slow-release film for treating oral ulcer and preparation method thereof |
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2018
- 2018-05-22 CN CN201810497352.0A patent/CN108542897A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5972906A (en) * | 1991-07-03 | 1999-10-26 | Hyal Pharmaceutical Corporation | Treatment of mucous membrane disease, trauma or condition and for the relief of pain thereof |
| CN1522687A (en) * | 2003-02-17 | 2004-08-25 | 北京泰瑞伟业科技有限公司 | Oral health product using adhesive material as carrier |
| CN204379821U (en) * | 2014-12-25 | 2015-06-10 | 第四军医大学唐都医院 | A kind of oral ulcer film paster |
| CN204446300U (en) * | 2015-02-03 | 2015-07-08 | 广东泰宝医疗科技股份有限公司 | A kind of composite medical dressing |
| CN104888265A (en) * | 2015-05-08 | 2015-09-09 | 四川大学 | Thermosensitive collagen-based composite hemostat gel and preparation method thereof |
| CN106109445A (en) * | 2016-06-22 | 2016-11-16 | 佛山市高明绿化纳新材料有限公司 | A kind of long-acting slow-release film for treating oral ulcer and preparation method thereof |
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