CN115054589B - Oral instant film agent containing L-borneol and preparation method thereof - Google Patents
Oral instant film agent containing L-borneol and preparation method thereof Download PDFInfo
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- CN115054589B CN115054589B CN202210609533.4A CN202210609533A CN115054589B CN 115054589 B CN115054589 B CN 115054589B CN 202210609533 A CN202210609533 A CN 202210609533A CN 115054589 B CN115054589 B CN 115054589B
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- borneol
- pva
- liquid medicine
- instant film
- oral
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- DTGKSKDOIYIVQL-QXFUBDJGSA-N (-)-borneol Chemical compound C1C[C@]2(C)[C@H](O)C[C@H]1C2(C)C DTGKSKDOIYIVQL-QXFUBDJGSA-N 0.000 title claims abstract description 66
- 229930006703 (-)-borneol Natural products 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 65
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 26
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract description 21
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229940041616 menthol Drugs 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- 239000012153 distilled water Substances 0.000 claims abstract description 11
- 235000011187 glycerol Nutrition 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 6
- 229920000136 polysorbate Polymers 0.000 claims abstract description 6
- 229950008882 polysorbate Drugs 0.000 claims abstract description 6
- 239000000796 flavoring agent Substances 0.000 claims abstract description 5
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
- 239000007788 liquid Substances 0.000 claims description 41
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 27
- 238000001035 drying Methods 0.000 claims description 20
- 229920000881 Modified starch Polymers 0.000 claims description 19
- 239000004368 Modified starch Substances 0.000 claims description 19
- 235000019426 modified starch Nutrition 0.000 claims description 19
- 239000011521 glass Substances 0.000 claims description 14
- 229940087305 limonene Drugs 0.000 claims description 14
- 235000001510 limonene Nutrition 0.000 claims description 14
- 238000000227 grinding Methods 0.000 claims description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 10
- 235000019202 steviosides Nutrition 0.000 claims description 10
- 238000005303 weighing Methods 0.000 claims description 10
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 8
- 229940013618 stevioside Drugs 0.000 claims description 8
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 6
- -1 PVA compound Chemical class 0.000 claims description 5
- 238000004140 cleaning Methods 0.000 claims description 5
- 238000005520 cutting process Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000003292 glue Substances 0.000 claims description 5
- 239000004570 mortar (masonry) Substances 0.000 claims description 5
- 238000004806 packaging method and process Methods 0.000 claims description 5
- 229920003023 plastic Polymers 0.000 claims description 5
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims description 5
- 229940068968 polysorbate 80 Drugs 0.000 claims description 5
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 5
- 238000002203 pretreatment Methods 0.000 claims description 5
- 238000002791 soaking Methods 0.000 claims description 5
- 238000003892 spreading Methods 0.000 claims description 5
- 230000007480 spreading Effects 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000004383 Steviol glycoside Substances 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- 235000019411 steviol glycoside Nutrition 0.000 claims description 2
- 229930182488 steviol glycoside Natural products 0.000 claims description 2
- 150000008144 steviol glycosides Chemical group 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 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000035876 healing Effects 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 11
- 239000002552 dosage form Substances 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 42
- 241000700159 Rattus Species 0.000 description 15
- 208000027418 Wounds and injury Diseases 0.000 description 15
- 206010052428 Wound Diseases 0.000 description 11
- 210000002200 mouth mucosa Anatomy 0.000 description 11
- 229930006000 Sucrose Natural products 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 239000012738 dissolution medium Substances 0.000 description 5
- 210000004400 mucous membrane Anatomy 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 240000000572 Blumea balsamifera Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 241000208838 Asteraceae Species 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000000396 limonene group Chemical group 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 231100000274 skin absorption Toxicity 0.000 description 1
- 230000037384 skin absorption Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61K9/7007—Drug-containing films, membranes or sheets
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Psychiatry (AREA)
- Nutrition Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Hospice & Palliative Care (AREA)
- Physiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides an oral instant film containing L-borneol and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, wherein the oral instant film comprises the following components in parts by weight: 0.5 to 1g of L-borneol, 0.4 to 0.8g of menthol, 10 to 15g of film forming material, 800.2 to 0.6g of polysorbate, 0.8 to 1.5g of glycerin, 50 to 60ml of distilled water, 0.3 to 0.5g of flavoring agent and 0.5 to 0.8g of disintegrating agent. The invention takes the L-borneol as a main medicine component to prepare the oral instant film, and solves the problems of complex preparation process, poor dosage form fitting degree, slow drug release and poor healing promotion effect.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to an oral instant film containing L-borneol and a preparation method thereof.
Background
The L-borneol is also called as blumea balsamifera tablet, which is white semitransparent flaky, blocky or granular crystal prepared by extracting and processing fresh leaves of blumea balsamifera of Compositae, has hard and brittle quality and is not easy to break when twisted by hands. The L-borneol has pungent and cool taste and has the medicinal effects of inducing resuscitation, refreshing mind, resisting inflammation, sterilizing, clearing heat, relieving pain and the like.
The preparations commonly used for treating the oral mucosa wounds comprise oral chewable tablets, buccal tablets, disintegrating tablets and the like, and have complex preparation process; friability due to dosage form limitations is large; poor fitting effect with oral mucosa; the release of the active ingredients is slow and the effect of promoting healing is poor.
The oral instant film is a light and thin medicine carrying film prepared by uniformly mixing medicine and a water-soluble polymer film forming material, and the film has the characteristics of no friability, good attaching effect with oral mucosa and the like. The prior art does not have researches on using the L-borneol as a main medicine component for preparing an oral instant film. At present, an oral instant film agent containing L-borneol, which has the advantages of simple preparation process, high adhesion degree with oral mucosa, quick drug release and good healing promoting effect, is needed.
Disclosure of Invention
(one) solving the technical problems
Aiming at the defects of the prior art, the invention provides the oral instant film containing the L-borneol and the preparation method thereof, and the L-borneol is used as a main medicine component to prepare the oral instant film, so that the problems of complex preparation process, poor preparation formulation laminating degree, slow drug release and poor healing promoting effect are solved.
(II) technical scheme
In order to achieve the above purpose, the invention is realized by the following technical scheme:
the oral instant film agent containing the L-borneol comprises the following components in parts by weight: 0.5 to 1g of L-borneol, 0.4 to 0.8g of menthol, 10 to 15g of film forming material, 800.2 to 0.6g of polysorbate, 0.8 to 1.5g of glycerin, 50 to 60ml of distilled water, 0.3 to 0.5g of flavoring agent and 0.5 to 0.8g of disintegrating agent.
Preferably, the film-forming material is PVA.
Preferably, the PVA is pretreated before being put into use, and the pretreatment method is as follows: modifying PVA by using etherified modified starch, wherein the mass ratio of the etherified modified starch to the PVA is (1.7-1.9): 8, preparing an etherified modified starch/PVA compound.
Preferably, the etherified modified starch is embedded with a penetration enhancer.
Preferably, the permeation enhancer is limonene.
Preferably, the flavoring agent is steviol glycoside.
Preferably, the disintegrant is low substituted hydroxypropyl cellulose.
The preparation method of the oral instant film containing the L-borneol comprises the following preparation steps:
s1, soaking PVA in 85% ethanol solution overnight, filtering, repeating the treatment on filter residues, and drying the filter residues to obtain refined PVA for later use;
s2, weighing the refined PVA, adding distilled water, and heating in a water bath to dissolve the PVA into a glue solution for later use;
s3, dissolving the main drugs of the L-borneol and menthol in a small amount of organic solvent for standby;
s4, weighing glycerol, polysorbate 80, stevioside and low-substituted hydroxypropyl cellulose, grinding uniformly in a mortar, adding PVA glue solution and dissolved main medicine, continuously grinding uniformly, preserving heat for 20-30 min at 45 ℃, and removing bubbles and part of ethanol for later use;
s5, cleaning and drying a glass plate, wiping with 75% ethanol solution, sucking 7.5-10 ml of the liquid medicine of the S4 by using a suction pipe, injecting the liquid medicine into the glass plate, spreading the liquid medicine on the glass plate uniformly, naturally and horizontally airing the liquid medicine to be semi-dry, drying the liquid medicine at the temperature of 40-50 ℃, standing the liquid medicine for 23-25 hours, demoulding, cutting the liquid medicine into corresponding sizes, sterilizing the liquid medicine by using ultraviolet rays, and packaging the liquid medicine in a plastic bag to obtain the oral instant film agent containing the L-borneol.
Preferably, the organic solvent in S3 is 75% -90% ethanol solution.
Preferably, the thickness of the chemical solution injected onto the glass plate in the step S5 is 0.3-0.4 mm.
(III) beneficial effects
The invention provides an oral instant film containing L-borneol and a preparation method thereof. Compared with the prior art, the method has the following beneficial effects:
when the oral instant film prepared by taking the L-borneol as a main medicine component is used for treating an oral mucosa wound, the oral instant film has no friability, has high fitting degree with the wound, is quickly dissolved under the action of saliva, and releases medicine after the L-borneol and menthol are dissolved out at the wound and nearby, and can quickly permeate due to good skin permeability of the L-borneol, so that the wound healing speed is accelerated. In addition, the preparation method is simple and easy to operate, and solves the problem of complicated existing technology.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a dissolution profile of an instant oral film comprising L-borneol according to example 2 of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention are clearly and completely described, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The embodiment of the invention provides the oral instant film containing the L-borneol and the preparation method thereof, and the L-borneol is used as a main medicine component to prepare the oral instant film, so that the problems of complex preparation process, poor dosage form fitting degree, slow drug release and poor healing promoting effect are solved.
Example 1
The oral instant film agent containing the L-borneol comprises the following components in parts by weight: 0.5g of L-borneol, 0.4g of menthol, 10g of PVA, 800.2g of polysorbate, 0.8g of glycerin, 50ml of distilled water, 0.3g of stevioside and 0.5g of low-substituted hydroxypropyl cellulose.
The preparation method of the oral instant film containing the L-borneol comprises the following preparation steps:
s1, soaking 10g of PVA in 85% ethanol solution overnight, filtering, repeating the treatment on filter residues for one time, and drying the filter residues at 60 ℃ to obtain refined PVA for later use;
s2, weighing the refined PVA, adding 50ml of distilled water, and heating in a water bath to dissolve the PVA into a glue solution for later use;
s3, dissolving 0.5g of L-borneol and 0.4g of menthol in a small amount of 75% ethanol solution for later use;
s4, weighing 0.8g of glycerin, 0.2g of polysorbate 80, 0.3g of stevioside and 0.5g of low-substituted hydroxypropyl cellulose, putting into a mortar, grinding uniformly, adding PVA glue solution and dissolved L-borneol, continuously grinding uniformly, preserving heat for 20min at 45 ℃, and removing bubbles and ethanol for later use;
s5, cleaning and drying a glass plate with the thickness of 5cm multiplied by 20cm, wiping with 75% ethanol solution, sucking 7.5ml of the liquid medicine of the S4 by using a suction pipe, injecting the liquid medicine into the glass plate, spreading the liquid medicine uniformly, enabling the liquid medicine to be 0.3mm thick, naturally and horizontally airing to be half-dry, drying at 40 ℃, standing for 23 hours, demoulding, cutting into corresponding sizes, carrying out ultraviolet sterilization treatment, and packaging in a plastic bag to obtain the oral instant film agent containing the L-borneol.
Example 2
The oral instant film agent containing the L-borneol comprises the following components in parts by weight: 0.8g of L-borneol, 0.6g of menthol, 13g of PVA, 800.4g of polysorbate, 1g of glycerin, 50ml of distilled water, 0.4g of stevioside and 0.65g of low-substituted hydroxypropyl cellulose.
The preparation method of the oral instant film containing the L-borneol comprises the following preparation steps:
s1, soaking 13g of PVA in 85% ethanol solution overnight, filtering, repeating the treatment on filter residues for one time, and drying the filter residues at 60 ℃ to obtain refined PVA for later use;
s2, weighing the refined PVA, adding 50ml of distilled water, and heating in a water bath to dissolve the PVA into a glue solution for later use;
s3, dissolving 0.8g of L-borneol and 0.6g of menthol in a small amount of 90% ethanol solution for later use;
s4, weighing 1g of glycerol, 0.4g of polysorbate 80, 0.4g of stevioside and 0.65g of low-substituted hydroxypropyl cellulose, putting into a mortar, grinding uniformly, adding PVA glue solution and dissolved L-borneol, continuously grinding uniformly, preserving heat for 30min at 45 ℃, and removing bubbles and ethanol for later use;
s5, cleaning and drying a glass plate with the length of 5cm multiplied by 20cm, wiping with 75% ethanol solution, sucking 10ml of the liquid medicine of the S4 by using a suction pipe, injecting the liquid medicine into the glass plate, spreading the liquid medicine uniformly, enabling the liquid medicine to be 0.4mm thick, naturally and horizontally airing to be semi-dry, drying the liquid medicine at 50 ℃, standing the liquid medicine for 25 hours, demoulding, cutting the liquid medicine into corresponding sizes, carrying out ultraviolet sterilization treatment, and packaging the liquid medicine in a plastic bag to obtain the oral instant film agent containing the L-borneol.
Example 3
The oral instant film agent containing the L-borneol comprises the following components in parts by weight: 1g of L-borneol, 0.8g of menthol, 15g of PVA, 800.6g of polysorbate, 1.5g of glycerin, 60ml of distilled water, 0.5g of stevioside and 0.8g of low-substituted hydroxypropyl cellulose.
The preparation method of the oral instant film containing the L-borneol comprises the following preparation steps:
s1, soaking 15g of PVA in 85% ethanol solution overnight, filtering, repeating the treatment on filter residues for one time, and drying the filter residues at 60 ℃ to obtain refined PVA for later use;
s2, weighing the refined PVA, adding 60ml of distilled water, and heating in a water bath to dissolve the PVA into a glue solution for later use;
s3, dissolving 1g of L-borneol and 0.8g of menthol in a small amount of 90% ethanol solution for later use;
s4, weighing 1.5g of glycerol, 0.6g of polysorbate 80, 0.5g of stevioside and 0.8g of low-substituted hydroxypropyl cellulose, putting into a mortar, grinding uniformly, adding PVA glue solution and dissolved L-borneol, continuously grinding uniformly, preserving heat for 20min at 45 ℃, and removing bubbles and ethanol for later use;
s5, cleaning and drying a glass plate with the length of 5cm multiplied by 20cm, wiping with 75% ethanol solution, sucking 10ml of the liquid medicine of the S4 by using a suction pipe, injecting the liquid medicine into the glass plate, spreading the liquid medicine uniformly, enabling the liquid medicine to be 0.4mm thick, naturally and horizontally airing to be semi-dry, drying the liquid medicine at 50 ℃, standing the liquid medicine for 25 hours, demoulding, cutting the liquid medicine into corresponding sizes, carrying out ultraviolet sterilization treatment, and packaging the liquid medicine in a plastic bag to obtain the oral instant film agent containing the L-borneol.
Example 4 differs from example 2 in that:
the PVA is pretreated before being put into use, and the pretreatment method comprises the following steps:
PVA was combined with etherified modified starch at 1.7:8, placing the mixture in a water bath, stirring at high temperature until the slurry is completely dissolved, and preparing a solution with the concentration of 6.5%;
and standing the solution for 24 hours, and drying, extruding, crushing and sieving the solution after the performance of the solution is stable to obtain the etherified modified starch/PVA compound.
Example 5 differs from example 2 in that:
the PVA is pretreated before being put into use, and the pretreatment method comprises the following steps:
PVA was combined with etherified modified starch at 1.8:8, placing the mixture in a water bath, stirring at high temperature until the slurry is completely dissolved, and preparing a solution with the concentration of 6.5%;
and standing the solution for 24 hours, and drying, extruding, crushing and sieving the solution after the performance of the solution is stable to obtain the etherified modified starch/PVA compound.
Example 6 differs from example 2 in that:
the PVA is pretreated before being put into use, and the pretreatment method comprises the following steps:
PVA was combined with etherified modified starch at 1.9:8, placing the mixture in a water bath, stirring at high temperature until the slurry is completely dissolved, and preparing a solution with the concentration of 6.5%;
and standing the solution for 24 hours, and drying, extruding, crushing and sieving the solution after the performance of the solution is stable to obtain the etherified modified starch/PVA compound.
Example 7 differs from example 5 in that:
the etherified modified starch is embedded with limonene, and the embedding method is as follows: heating and expanding etherified modified starch for 0.45h to form expanded starch;
adding a limonene ethanol solution under the condition of heat preservation and stirring, cooling to room temperature after reacting for 5 hours, recrystallizing for 8 hours, centrifuging, washing and drying to obtain a primary finished product, wherein the content of limonene is 5mg/g;
stirring the primary product in a dry state, uniformly spraying a sucrose aqueous solution with the concentration of 20% on the surface of the primary product by using a sprayer, and drying at normal temperature to obtain the etherified modified starch embedded with the limonene, wherein the content of the sucrose is 15mg/g.
Comparative example 1
The difference from example 2 is that: deleting the component of the L-borneol.
Comparative example 2
The difference from example 7 is that: the component of the etherified modified starch is azone.
Performance test
1. Dissolution test
Sample 3 of example 2 was taken and subjected to dissolution and release measurement (chinese pharmacopoeia 2015, general rule 0931, fourth method) at a rotation speed of 100r/min at 900ml of phosphate buffer solution pH 6.8 as a dissolution medium. Starting timing when the oral instant membrane containing L-borneol is contacted with the dissolution medium, taking 5ml of solution at 0.5, 1, 3, 5, 10, 15, 20 and 30 mm, and immediately supplementing the dissolution medium heated to (37+/-0.5) DEG C with the same volume. 1mL of internal standard solution methyl salicylate (1.401 mg.mL-1) is added after the sample liquid with the same volume is taken, ethyl acetate is added for extraction, the volume is fixed, 1 mu L of extract liquid is precisely sucked for sample injection analysis, and the L-borneol is taken as an investigation index, so that the peak area is recorded. The concentration and the cumulative dissolution rate of each sampling point are calculated by an internal standard method, and the result is shown in figure 1. From the figure, the oral instant membrane containing the L-borneol begins to dissolve the medicine after being dissolved into the dissolution medium, and the medicine is almost completely dissolved within 5 minutes.
2. Test of treatment effect on rats with damaged oral mucosa
And (3) molding:
rats were divided into 5 groups (no administration group a, example 1 group B, example 2 group C, example 3 group D, example 7 group E, comparative example 1 group F, comparative example 2 group G), 20 rats each were anesthetized with 10% chloral hydrate (3 mL/kg), fixed to an operating table, placed in a supine position, the upper and lower jaws were opened with hemostats, one-sided cheek pouch was pulled out with flat-tooth forceps, and a 10mmol/L methyl viologen solution was slowly and evenly fan-injected with a 5-gauge skin test needle 0.25mL at about 8mm below the cheek pouch mucosa, and 3s were scalded with a preformed iron nail having a temperature of 100 ℃ and a diameter of about 5mm at the injection site, and lip wetting was observed, and swelling were visible in the cheek, i.e., molding was successful.
The test method comprises the following steps:
B. c, D, E, F groups were attached to the lesion of the oral mucosa one at a time, and the oral mucosa healing condition of the rats was visually observed on days 1, 3, 5, 7, 9 and 15 twice a day, and the number of healed rats was counted, and the healing rate was calculated, and the test data was recorded in table 1 below.
TABLE 1 comparison of the number of dental ulcer healing in rats of each group
3. PVA performance test
The thermal stability of the PVA in example 2 and examples 4 to 6 was examined.
The thermal stability of the PVA in examples 4 to 6 was improved by 25.7%, 27.2% and 26.6% respectively compared to example 2, as a result of the test using a thermal shrinkage tester (RSY-R2 of Labthink).
Analysis of test results
As can be seen in connection with fig. 1: the oral instant membrane containing the L-borneol begins to dissolve the medicine after being dissolved into a dissolution medium, and the medicine is almost completely dissolved in 5 minutes, which indicates that the oral instant membrane has excellent drug release property and can rapidly act on mucous membrane wounds.
As can be seen from table 1:
1. the B, C, D group has earlier healing time of the mucous membrane injury compared with the group A without administration, especially the group D has 1 rat mucous membrane injury healing at the 5 th day of administration, the B, C, D administration group has healed rats at the 7 th day, and the healing rate of the rats reaches 80% -90% by the 15 th day. The oral instant film agent containing the L-borneol has the effect of improving the healing rate of oral mucosa injury compared with the A group and the F group.
2. Compared with the group D, the group E has 1 rat mucous membrane injury healing at the 3 rd day of administration, when the oral instant film agent of the group E is contacted with the rat mucous membrane wound, the L-borneol and the menthol can quickly release the medicine, and the limonene can promote the permeation of the medicine, and the permeation pressure difference can be formed after the sucrose is dissolved in the oral cavity, so that the permeation of the L-borneol and the menthol can be promoted, the permeation of the limonene can be promoted, the wound healing speed of the rat is accelerated, the number of the healed rats at the 3 rd day is increased, and the healing time of the rat is shortened.
3. Compared with the group G in which limonene is replaced by azone, the group E rats have shorter healing time and faster healing speed, which indicates that the limonene has good synergistic effect with each component in the formula of the invention, and the effect is reduced after the limonene is replaced by azone.
In summary, compared with the prior art, the method has the following beneficial effects:
1. when the oral instant film prepared by taking the L-borneol as a main medicine component is used for treating an oral mucosa wound, the oral instant film has no friability, has high fitting degree with the wound, is quickly dissolved by a PVA film under the action of saliva, and releases medicine after the L-borneol and the menthol are dissolved out at the wound and nearby, and can promote the wound to heal quickly due to good skin permeability and medicine property of the L-borneol. In addition, the preparation method is simple and easy to operate, and solves the problem of complicated existing technology.
2. Menthol has the effects of relieving pain, diminishing inflammation and the like, and the main component menthol also has the effect of promoting skin absorption, can accelerate the penetration of menthol and L-borneol into the skin, and the menthol and the L-borneol have synergistic effect so as to achieve good healing promoting effect.
3. The PVA is pretreated to improve the stability of the PVA, so that the stability of the prepared oral instant film is improved.
4. The etherified modified starch used to modify PVA has limonene embedded therein and is treated with an aqueous sucrose solution. The limonene, the L-borneol and the menthol have the synergistic permeation rate effect, and the sucrose not only can improve the taste of the oral instant film, but also can form osmotic pressure difference at the wound of the oral mucosa after being dissolved, and promote the permeation of the three components, so that the limonene, the L-borneol, the menthol and the sucrose have synergistic effect, and the synergistic effect is achieved for the healing-promoting effect of the oral instant film.
The above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (6)
1. The oral instant film containing the L-borneol is characterized by comprising the following components in parts by weight: 0.5 to 1g of L-borneol, 0.4 to 0.8g of menthol, 10 to 15g of film forming material, 0.2 to 0.6g of polysorbate, 0.8 to 1.5g of glycerin, 50 to 60ml of distilled water, 0.3 to 0.5g of flavoring agent and 0.5 to 0.8g of disintegrating agent; the film forming material is PVA; the disintegrating agent is low-substituted hydroxypropyl cellulose;
the PVA is pretreated before being put into use, and the pretreatment method comprises the following steps: modifying PVA by using etherified modified starch, wherein the mass ratio of the etherified modified starch to the PVA is (1.7-1.9): 8, preparing an etherified modified starch/PVA compound.
2. The l-borneol containing oral instant film according to claim 1, wherein the etherified modified starch is embedded with limonene.
3. The l-borneol containing oral instant film according to claim 1, wherein the flavoring agent is steviol glycoside.
4. A process for preparing an instant film agent for oral cavity containing l-borneol according to any one of claims 1 to 3, which comprises the following steps:
s1, soaking PVA in 85% ethanol solution overnight, filtering, repeating the treatment on filter residues, and drying the filter residues to obtain refined PVA for later use;
s2, weighing the refined PVA, adding distilled water, and heating in a water bath to dissolve the PVA into a glue solution for later use;
s3, dissolving the main drugs of the L-borneol and menthol in a small amount of organic solvent for standby;
s4, weighing glycerol, polysorbate 80, stevioside and low-substituted hydroxypropyl cellulose, grinding uniformly in a mortar, adding PVA glue solution and dissolved main medicine, continuously grinding uniformly, preserving heat for 20-30 min at 45 ℃, and removing bubbles and part of ethanol for later use;
s5, cleaning and drying a glass plate, wiping with 75% ethanol solution, sucking 7.5-10 ml of the liquid medicine of the S4 by using a suction pipe, injecting the liquid medicine into the glass plate, spreading the liquid medicine on the glass plate uniformly, naturally and horizontally airing the liquid medicine to be semi-dry, drying the liquid medicine at the temperature of 40-50 ℃, standing the liquid medicine for 23-25 hours, demoulding, cutting the liquid medicine into corresponding sizes, sterilizing the liquid medicine by using ultraviolet rays, and packaging the liquid medicine in a plastic bag to obtain the oral instant film agent containing the L-borneol.
5. The method for preparing the oral instant film containing the L-borneol according to claim 4, wherein the organic solvent in the step S3 is 75-90% ethanol solution.
6. The method for preparing an instant oral film containing L-borneol according to claim 4, wherein the thickness of the liquid medicine injected into the glass plate in the step S5 is 0.3-0.4 mm.
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| WO2001022934A2 (en) * | 1999-09-24 | 2001-04-05 | Yng Wong Quing Non | Delivery of small doses of ingestible treatments |
| CN101669922A (en) * | 2008-09-11 | 2010-03-17 | 北京科信必成医药科技发展有限公司 | Medicament carrying film capable of being absorbed by oral cavity and preparation method thereof |
| CN112618518A (en) * | 2021-01-18 | 2021-04-09 | 江苏谛奇医药科技有限公司 | Lurasidone hydrochloride oral instant membrane preparation and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001022934A2 (en) * | 1999-09-24 | 2001-04-05 | Yng Wong Quing Non | Delivery of small doses of ingestible treatments |
| CN101669922A (en) * | 2008-09-11 | 2010-03-17 | 北京科信必成医药科技发展有限公司 | Medicament carrying film capable of being absorbed by oral cavity and preparation method thereof |
| CN112618518A (en) * | 2021-01-18 | 2021-04-09 | 江苏谛奇医药科技有限公司 | Lurasidone hydrochloride oral instant membrane preparation and preparation method thereof |
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