CN108379580A - A kind of 5-ALA gel combination and its application - Google Patents
A kind of 5-ALA gel combination and its application Download PDFInfo
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- CN108379580A CN108379580A CN201810260017.9A CN201810260017A CN108379580A CN 108379580 A CN108379580 A CN 108379580A CN 201810260017 A CN201810260017 A CN 201810260017A CN 108379580 A CN108379580 A CN 108379580A
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- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000003745 diagnosis Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000011159 matrix material Substances 0.000 claims abstract description 9
- 210000004400 mucous membrane Anatomy 0.000 claims abstract description 8
- 239000004909 Moisturizer Substances 0.000 claims abstract description 7
- 239000000853 adhesive Substances 0.000 claims abstract description 7
- 230000001070 adhesive effect Effects 0.000 claims abstract description 7
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 7
- 230000001333 moisturizer Effects 0.000 claims abstract description 7
- 239000003002 pH adjusting agent Substances 0.000 claims abstract description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 9
- 235000011187 glycerol Nutrition 0.000 claims description 9
- 235000002906 tartaric acid Nutrition 0.000 claims description 9
- 239000011975 tartaric acid Substances 0.000 claims description 9
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 8
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 8
- UTUUIUQHGDRVPU-UHFFFAOYSA-K aluminum;2-aminoacetate;dihydroxide;hydrate Chemical group O.[OH-].[OH-].[Al+3].NCC([O-])=O UTUUIUQHGDRVPU-UHFFFAOYSA-K 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 6
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 229940005605 valeric acid Drugs 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 3
- 239000004745 nonwoven fabric Substances 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 2
- 210000004877 mucosa Anatomy 0.000 abstract description 4
- 229960002749 aminolevulinic acid Drugs 0.000 abstract description 3
- QUCHWTCTBHQQDU-UHFFFAOYSA-N 2-amino-4-oxopentanoic acid Chemical class CC(=O)CC([NH3+])C([O-])=O QUCHWTCTBHQQDU-UHFFFAOYSA-N 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 210000000214 mouth Anatomy 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003504 photosensitizing agent Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000002428 photodynamic therapy Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 3
- 239000011505 plaster Substances 0.000 description 3
- 101000642224 Apomastus schlingeri U1-cyrtautoxin-As1d Proteins 0.000 description 2
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical compound CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 2
- -1 Hydroxyl aluminium Chemical compound 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 229950003776 protoporphyrin Drugs 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 1
- 208000034493 Mucous membrane disease Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
-
- 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
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The present invention provides a kind of 5 aminolevulinic acid gel combinations, it is that the supplementary material matched by following weight is prepared：51 part of aminolevulinic acids, 67 parts of matrix, 0.2 0.5 parts of crosslinking agent, 30 50 parts of moisturizer, 2.5 parts of transdermal agent, 0.1 0.25 parts of pH adjusting agent, 50 parts of water.The present invention also provides a kind of gel adhesives and application thereof.The gel combination of the present invention has good release and percutaneous abilities, and good biocompatibility, non-stimulated to mucosa, and diagnosis and treatment to mucous membrane of mouth canceration have good result.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of 5-ALA gel combination and its application.
Background technology
Light dynamic study has pushed the development of biology and medicine, then derived diagnosing tumor, treatment new skill
Art --- light power diagnosis (Photodynamic diagnosis, PDD) and optical dynamic therapy (Photodynamic
Therapy, PDT), the two is use in conjunction photosensitizer and respective sources, by photodynamics reaction to tumour carry out diagnosis or
The technology for the treatment of.Currently, the tumour that PDT has become after the tumours traditional remedies such as operation, radiotherapy, chemotherapy and immunotherapy is new
Therapy.
Light power diagnosis and treatment are with wound is small, toxic side effect is small, selectivity is good, favorable repeatability, can protect appearance
And the advantages that vitals function, increasingly become a kind of tumour new tool having much foreground.For older, constitution is poor, merges
Other organic diseases etc. are not resistant to or are reluctant to undergo surgery, radiotherapy, chemotherapy patient, PDT is also a kind of to substitute well
Treatment means.
5-ALA (5-aminolevulinic acid, 5-ALA) is clinical most common photosensitizer, is a kind of
The natural amino acid synthesized in animals and plants mitochondria is the precursor of porphyrin, ferroheme.Under normal circumstances, human body passes through cell
The negative feedback inhibition ALA synzyme of interior content of hemachrome, to control the production quantity of ALA.After exogenous ALA enters human body,
It can be absorbed and added up by the cell of active proliferation such as tumor cells selectivity, be converted into protoporphyrin IX, protoporphyrin IX in the cell
Fluorescence is generated after the irradiation of the light of specific wavelength and is used for diagnosing and treating.
5-ALA is as a kind of endogenous photo-dynamical medicine, by the extensive favor of researchers, due to 5- ammonia
Base ketone valeric acid is water-soluble substances, and administration route is various, can be administered systemically or local administration.But the 5- amino developed at present
Ketone valeric acid product is mostly emulsion or solution, predominantly takes orally, is injected intravenously mode medication, but when it is in the certain mucous membrane portions of body
When the medication of position, due to the stimulated meeting secreting mucus of mucous membrane, coated medicament is watered down or even washed away so as to mucosa such as mouth
Chamber, nasal cavity, the diagnosing and treating of urethral mucosa are ineffective.
A kind of light comprising by 5-ALA or derivatives thereof of the patent report of Publication No. CN102670577A
Quick dose of composition, the penetrating agent used include dimethyl sulfoxide, have bio-toxicity, are unsuitable for human body use, and oral cavity is glutinous
Film position is to be constantly in moisture state, which does not consider the stickiness of gel under this specific condition.
Invention content
To solve the above-mentioned problems, it the purpose of the present invention is to provide a kind of 5-ALA gel combination and its answers
With.
The present invention provides a kind of 5-ALA gel combinations, it is prepared by the supplementary material that following weight matches
It forms：
1 part of 5-ALA, 6-7 parts of matrix, 0.2-0.5 parts of crosslinking agent, 30-50 parts of moisturizer, 2.5 parts of transdermal agent,
0.1-0.25 parts of pH adjusting agent, 50 parts of water.
Wherein, it is that the supplementary material matched by following weight is prepared：
1 part of 5-ALA, 6 parts of matrix, 0.2 part of crosslinking agent, 30 parts of moisturizer, 2.5 parts of transdermal agent, pH adjusting agent
0.1 part, 50 parts of water.
Wherein, the matrix is at least one of Sodium Polyacrylate, hydroxymethyl cellulose；
The crosslinking agent is Dihydroxyaluminium Aminoacetate；
The pH adjusting agent is tartaric acid；
The moisturizer is glycerine；
The transdermal agent is propylene glycol.
Wherein, the Sodium Polyacrylate is NP700.
Wherein, it is that the supplementary material matched by following weight is prepared：
1 part of 5-ALA, 5 parts of Sodium Polyacrylate, 2 parts of hydroxymethyl cellulose, 0.2 part of Dihydroxyaluminium Aminoacetate, 30 parts of glycerine, third
2.5 parts of glycol, 0.1 part of tartaric acid, 50 parts of water.
The present invention also provides the preparation methods of above-mentioned gel combination, it includes the following steps：
(1) supplementary material is weighed by weight ratio；
(b) by NP700 and glycerine mixing, hydroxymethyl cellulose, Dihydroxyaluminium Aminoacetate and propylene glycol, stirring is added；Then it is added
5-ALA is eventually adding aqueous tartaric acid solution, is sufficiently stirred into sticky shape semisolid fluid.
The present invention also provides a kind of gel adhesives, are made of supporting layer, gel layer and separation layer, it is characterised in that：Institute
Gel layer is stated to be filled by above-mentioned gel combination.
Wherein, the material of the supporting layer is medical non-woven fabrics；The material of the separation layer is release paper.
The present invention also provides above-mentioned gel combination, gel adhesives in the photochemical drugs for preparing diagnosing tumor, treatment
In purposes.
Wherein, the tumour is superficial place tumour；Wherein, the tumour is mucous membrane of mouth canceration.
The 5-ALA gel combination of the present invention, bright in color, matrix are uniform, adhesiveness is good, to photosensitizer 5-
Aminolevulinic acid has package, release and percutaneous abilities, and good biocompatibility well, counterpart non-stimulated to mucosa
The diagnosis and treatment of chamber mucous membrane canceration have good result.
Obviously, the above according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific implementation mode of form by the following examples remakes further specifically the above of the present invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on the above of the present invention
The technology realized all belongs to the scope of the present invention.
Specific implementation mode
It is described further below with embodiment, but the present invention is not limited to these embodiments.
Experiment reagent and instrument used in the present invention is as follows：
Glycerine (Alfa Aesar, 36646), NP700 (Japanese showa Denko K.K companies), sodium cellulose glycolate
(Tokyo chemical conversion industry Zhu Shi people's communes, C0603), Dihydroxyaluminium Aminoacetate (ladder is uncommon to fall in love with extra large chemical conversion industry Development Co., Ltd, A1200), third
Glycol (Tokyo chemical conversion industry Zhu Shi people's communes, P0485), tartaric acid (Tokyo chemical conversion industry Zhu Shi people's communes, T0025), medical non-woven
Cloth (Wenzhou Ao Qiboaisi), release paper (Wenzhou in length and breadth paper industry).
The preparation of 1 inventive gel composition of embodiment
5g NP700 are uniformly mixed with the mixed liquor stirring at low speed of 30g glycerine, 2g hydroxymethyl celluloses are added, 0.2g is sweet
Hydroxyl aluminium and 2.5g propylene glycol continue stirring at low speed；Then be added 1g 5-ALAs, be eventually adding tartaric acid 0.1g and
Water 50g is sufficiently stirred into sticky shape semisolid fluid, you can.
The preparation of 2 inventive gel patch of embodiment
5g NP700 are uniformly mixed with the mixed liquor stirring at low speed of 30g glycerine, 2g hydroxymethyl celluloses are added, 0.2g is sweet
Hydroxyl aluminium and 2.5g propylene glycol continue stirring at low speed；Then be added 1g 5-ALAs, be eventually adding tartaric acid 0.1g and
Water 50g is sufficiently stirred into sticky shape semisolid fluid, is spread evenly across on non-woven fabrics, covers release paper, be pressed into required thickness
Thin slice is placed at room temperature for for 24 hours, is punched, is packed to obtain the final product.
Beneficial effects of the present invention are illustrated below by way of test example：
The screening experiment of 1 inventive gel composition of test example
The present invention has investigated each ingredient in host material respectively, dosage to gel rubber plaster adhesion strength, Tu malleability and its
The influence of residual quantity on moistening skin
Wherein, adhesion strength, Tu malleability are detected with rheometer, and residual quantity is with the naked eye evaluated.
Specific the selection result is as follows：
The screening test of 1. different amounts component of table
As it can be seen that the amounts of components of selection serial number 3-5,8-10,16,17,20,21, it just can guarantee that gel rubber plaster adhesion strength is strong, Tu
Malleability is good and its residual quantity on moistening skin is more, and gelling performance is good, especially No. 3 consumption proportion best results.And it selects
Other consumption proportions are selected, then gelling performance is poor.
The effect expedition of 2 inventive gel composition of test example
The molding gel adhesive bright in color of the present invention, matrix is uniform, adhesiveness is preferable, while to photosensitizer 5- amino ketones
Valeric acid has package (the maximum big 0.1g/ml of package amount) well, investigates its release performance, method and result are as follows：
The gel rubber plaster for wrapping photosensitizer 5-ALA is positioned in the sample cell equipped with 10ml PBS, constant temperature 37
Degree, adjusting magnetic agitation rotating speed are 250rpm, and 0.2ml was taken from sample cell at 1,5,10,20,40,60,80,100 minute respectively
Sample, while supplementing the PBS of 0.2ml, then the fluorescence intensity of determination sample, determines its release performance.
It the results are shown in Table 2.
2. release performance of table is investigated
| Release time (min) | Discharge percentage (%) |
| 1 | 5 |
| 5 | 15 |
| 10 | 30 |
| 20 | 40 |
| 40 | 45 |
| 60 | 50 |
| 80 | 52 |
| 100 | 55 |
As it can be seen that inventive gel patch release performance is good, after 1h close to maximum releasing dosage is reached, illustrate it thoroughly
Skin is functional.
The biological safety of 3 inventive gel patch of test example
Cells survival rate by detecting oral cavity normal epithelium cell NOK-SI evaluates inventive gel composition in vitro
To the cytotoxicity of normal cell.
Well-grown cell is collected respectively, is configured to cell suspension, while being adjusted its cell density and being inoculated in 96 orifice plates
In, wait for 4~6h cells it is adherent after be added 100 μ l various concentrations gel combination (2,4,8gml-1), 37 DEG C be incubated for 24 hours,
20 μ l MTT are added after 48h, 72h, are incubated 4h, DMSO (dimethyl sulfoxide (DMSO)) 150 μ l are added, detect the absorbance of 570nm wavelength
Value.Toxicity of the detection material to cell in vitro.
As a result IC of the gel combination to normal cell NOK-SI cells50Value is more than 10gml-1, illustrate to normal thin
The small toxicity of born of the same parents has good biological safety.
And water is added to be 50g in claimed composition, it is equivalent to 0.1g/ml concentration, is far below toxotest
Concentration, illustrate that the concentration in composition is even more safe and reliable.
The application of 4 inventive gel patch of test example
Fluorescence is generated using the purplish blue light excitation that wavelength is 375~440nm, is used for the diagnosis of mucous membrane of mouth canceration, simultaneously
It is may result from when being irradiated with feux rouges (635nm) by base oxygen, for the prevention and treatment before cancer.
The specific method is as follows：In diagnoses and treatment, the gel paster is directly affixed on mucous membrane disease damage area；ALA is in body
Inside being converted to endogenous PP Ⅸ its distribution has highly selective, and the faster cell transformation rates of certain proliferation are especially strong, thus cell
The content of interior PP Ⅸ can use the purplish blue light that wavelength is 375~440nm to excite production also compared with other cells height using this principle
Raw fluorescence is used for the diagnosis of mucous membrane of mouth canceration in combination with clinical manifestation if lesion region fluorescence is very strong；If without cancer
Becoming also prompt has the value-added cell of more exception, can enter clinical observation in advance and prevent canceration；If make a definite diagnosis to use simultaneously
Feux rouges (635nm) may result from being treated by base oxygen when irradiating.
In addition, inventive gel patch also is adapted for the diagnosis and treatment of other table superficial parts position cancer.
Claims (10)
1. a kind of 5-ALA gel combination, it is characterised in that：It is the supplementary material matched by following weight prepare and
At：
1 part of 5-ALA, 6-7 parts of matrix, 0.2-0.5 parts of crosslinking agent, 30-50 parts of moisturizer, 2.5 parts of transdermal agent, pH tune
Save 0.1-0.25 parts of agent, 50 parts of water.
2. gel combination according to claim 1, it is characterised in that：It is prepared by the supplementary material that following weight matches
It forms：
1 part of 5-ALA, 6 parts of matrix, 0.2 part of crosslinking agent, 30 parts of moisturizer, 2.5 parts of transdermal agent, 0.1 part of pH adjusting agent,
50 parts of water.
3. gel combination according to claim 1 or 2, it is characterised in that：
The matrix is at least one of Sodium Polyacrylate, hydroxymethyl cellulose；
The crosslinking agent is Dihydroxyaluminium Aminoacetate；
The pH adjusting agent is tartaric acid；
The moisturizer is glycerine；
The transdermal agent is propylene glycol.
4. gel combination according to claim 3, it is characterised in that：
The Sodium Polyacrylate is NP700.
5. gel combination according to any one of claims 1-4, it is characterised in that：It is matched by following weight
Supplementary material is prepared：
1 part of 5-ALA, 5 parts of Sodium Polyacrylate, 2 parts of hydroxymethyl cellulose, 0.2 part of Dihydroxyaluminium Aminoacetate, 30 parts of glycerine, propylene glycol
2.5 parts, 0.1 part of tartaric acid, 50 parts of water.
6. the preparation method of gel combination described in claim 5, it is characterised in that：It includes the following steps：
(1) supplementary material is weighed by weight ratio；
(b) by NP700 and glycerine mixing, hydroxymethyl cellulose, Dihydroxyaluminium Aminoacetate and propylene glycol, stirring is added；Then 5- ammonia is added
Base ketone valeric acid, is eventually adding aqueous tartaric acid solution, is sufficiently stirred into sticky shape semisolid fluid.
7. a kind of gel adhesive is made of supporting layer, gel layer and separation layer, it is characterised in that：The gel layer is wanted by right
The gel combination described in 1-5 any one is asked to fill.
8. gel adhesive according to claim 7, it is characterised in that：The material of the supporting layer is medical non-woven fabrics；Institute
The material for stating separation layer is release paper.
9. the gel adhesive described in gel combination, claim 7-8 described in claim 1-5 any one is preparing tumour
Purposes in diagnosis, the photochemical drugs treated.
10. purposes according to claim 9, it is characterised in that：The tumour is superficial place tumour；Wherein, described swollen
Tumor is mucous membrane of mouth canceration.
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| CN108379580B (en) | 2021-03-12 |
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