CN103717215A - 过敏性鼻炎的治疗剂 - Google Patents
过敏性鼻炎的治疗剂 Download PDFInfo
- Publication number
- CN103717215A CN103717215A CN201280028688.3A CN201280028688A CN103717215A CN 103717215 A CN103717215 A CN 103717215A CN 201280028688 A CN201280028688 A CN 201280028688A CN 103717215 A CN103717215 A CN 103717215A
- Authority
- CN
- China
- Prior art keywords
- ala
- light
- allergic rhinitis
- therapeutic agent
- pdt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 206010039085 Rhinitis allergic Diseases 0.000 title claims abstract description 49
- 201000010105 allergic rhinitis Diseases 0.000 title claims abstract description 49
- 239000003814 drug Substances 0.000 title claims abstract description 35
- 229940124597 therapeutic agent Drugs 0.000 title claims abstract description 30
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims abstract description 68
- 238000002428 photodynamic therapy Methods 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 235000015110 jellies Nutrition 0.000 claims abstract description 4
- 239000008274 jelly Substances 0.000 claims abstract description 4
- 239000002674 ointment Substances 0.000 claims abstract description 4
- 210000003928 nasal cavity Anatomy 0.000 claims description 16
- 239000011248 coating agent Substances 0.000 claims description 11
- 238000000576 coating method Methods 0.000 claims description 11
- 239000004615 ingredient Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 abstract description 18
- 230000005284 excitation Effects 0.000 abstract description 7
- 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 abstract description 4
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 229950003776 protoporphyrin Drugs 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 229960002749 aminolevulinic acid Drugs 0.000 abstract 4
- 238000009825 accumulation Methods 0.000 abstract 1
- 238000011282 treatment Methods 0.000 description 26
- 210000002850 nasal mucosa Anatomy 0.000 description 21
- 201000010927 Mucositis Diseases 0.000 description 20
- -1 hydroxyl radical free radical Chemical class 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- 238000002560 therapeutic procedure Methods 0.000 description 15
- 230000001678 irradiating effect Effects 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000004065 semiconductor Substances 0.000 description 7
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 206010048908 Seasonal allergy Diseases 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229920000742 Cotton Polymers 0.000 description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000013307 optical fiber Substances 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- 241001597008 Nomeidae Species 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000000586 desensitisation Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000158526 Nasalis Species 0.000 description 2
- 102000012547 Olfactory receptors Human genes 0.000 description 2
- 108050002069 Olfactory receptors Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 102000018727 5-Aminolevulinate Synthetase Human genes 0.000 description 1
- 108010052384 5-Aminolevulinate Synthetase Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 235000019737 Animal fat Nutrition 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- HNBPGMZUKDCQEE-UWTATZPHSA-N D-alanyl phosphate Chemical compound C[C@@H](N)C(=O)OP(O)(O)=O HNBPGMZUKDCQEE-UWTATZPHSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- DEFJQIDDEAULHB-IMJSIDKUSA-N L-alanyl-L-alanine Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(O)=O DEFJQIDDEAULHB-IMJSIDKUSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000026344 Nasal disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000030880 Nose disease Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical class [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000004446 light reflex Effects 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000018389 neoplasm of cerebral hemisphere Diseases 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007811 spectroscopic assay Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
- F04C—ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT PUMPS
- F04C2270/00—Control; Monitoring or safety arrangements
- F04C2270/04—Force
- F04C2270/042—Force radial
- F04C2270/0421—Controlled or regulated
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Otolaryngology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Immunology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供一种非侵袭性、几乎没有副作用和患者肉体上的痛苦、能安全且简便地治疗过敏性鼻炎的治疗剂。本发明提供5-氨基乙酰丙酸-光动力学疗法(ALA-PDT)用的过敏性鼻炎的治疗剂,其含有5-氨基乙酰丙酸(ALA)或其衍生物或者它们的盐作为有效成分,在照射400nm~700nm的波长的光的ALA-PDT中使用,本发明特别地提供能够局部涂布的溶液型、水溶性软膏溶解型或胶冻剂溶解型等的过敏性鼻炎的治疗剂。该治疗剂无需在ALA-PDT之前进行5-氨基乙酰丙酸-光动力学诊断(ALA-PDD),该ALA-PDD是照射380nm~420nm的波长的激发光,检测发射出610nm~650nm的波长的光的原卟啉IX(PpIX)蓄积部位。
Description
技术领域
本发明涉及一种过敏性鼻炎的治疗剂,其含有5-氨基乙酰丙酸(以下也称为“ALA或δ-氨基乙酰丙酸”)或其衍生物或者它们的盐(以下也将它们总称为“ALA类”)作为有效成分,在照射400nm~700nm、优选625nm~640nm的波长的光的5-氨基乙酰丙酸-光动力学疗法(以下也称为“ALA-PDT”)中使用。
过敏性鼻炎是因为体内的自身免疫系统对外部环境中的原因物质作出反应而引起的,作为原因物质,已知灰尘、霉菌、花粉等。
作为以花粉症为代表的过敏性鼻炎的治疗法,已知药剂疗法、脱敏疗法、基于使用激光的下鼻甲烧灼的手术疗法等。药剂疗法中使用类固醇性抗炎症剂、免疫抑制剂、抗组胺剂等,但已知在副作用、效果方面存在问题。例如问题在于,类固醇性抗炎症剂具有肾上腺萎缩、机能障碍、胃溃疡等副作用(例如参照非专利文献1)、免疫抑制剂具有感染症等副作用(例如参照非专利文献2)、抗组胺剂具有倦怠感、困倦、晕眩等副作用。另外,已知抗组胺剂与类固醇性抗炎症剂、免疫抑制剂相比,在效果方面有所不足。
另外,已知脱敏疗法是确定与过敏有关的抗原、通过将该抗原给药至皮内来诱导脱敏、从而仅抑制对于所要的抗原有特异性的免疫反应的方法,但需要几个月~几年的时间才能体现出足够的效果。还已知存在因为将作为过敏原因的抗原全身性地直接给药而导致过敏性休克等的危险性,需要从少量开始逐渐增加给药量。即,脱敏疗法的问题在于,不仅需要长期治疗,而且伴有注射对患者造成的痛苦。
另外,基于使用激光的下鼻甲烧灼的手术疗法的问题在于,不仅给过敏性鼻炎患者带来肉体上的痛苦,而且不是根本性地治疗过敏性鼻炎的方法。
另一方面,近年来开发出了PDT,PDT是给予对光作出反应的化合物、通过照射光来治疗目标部位的方法。PDT的治疗简便,机体侵袭性小,能保留器官等,因此近年来作为考虑到生活质量(QualityOf Life;QOL)的新型癌症治疗法受到关注。
已知PDT中使用的药剂之一的ALA是动物、植物、菌类中广泛存在的色素生物合成通路的中间体,通常在5-氨基乙酰丙酸合成酶的作用下由琥珀酰基CoA和甘氨酸生物合成。已知ALA本身虽然没有光感受性,但在细胞内在血红素生物合成通路的一系列的酶组的作用下代谢活化成原卟啉IX(以下也称为“PpIX”),直接特异性地聚集于肿瘤组织、新生血管,如果对该PpIX聚集部位照射激光,则在通过光的激发而生成的以单线态氧、羟基自由基、超氧化物等为代表的活性氧物质的作用下,癌细胞变性·坏死。
1986年,加拿大皇后大学肯尼迪教授报道,通过涂布ALA、照射光,能进行皮肤癌的治疗(例如参照非专利文献3),自此以后,报道了使用ALA对各种部位的病变部等的诊断及治疗方法,例如如果将ALA类给药至体内,则由ALA类衍生的PpIX蓄积在癌症处,通过光照射而发出荧光,提出了基于该发现而开发的肿瘤诊断剂等(例如参照专利文献1、2)。
另外,PpIX如果受到波长410nm附近的激发光,则发出在波长636nm处具有峰的红色荧光,因此ALA类被用于基于5-氨基乙酰丙酸-光动力学诊断(ALA-PDD)进行的肿瘤诊断,并且也期待在脑肿瘤、膀胱癌的诊断、贫血预防等中的应用。
专利文献1:日本专利第2731032号公报
专利文献2:日本专利特开2006-124372号公报
非专利文献1:小儿科临床 过敏疾病、池泽善郎、日本小儿医事出版社、1998
非专利文献2:综合临床 抗过敏药、福中秀典等、永井书店、1997
非专利文献3:J.C Kennedy,R.H Pottier和DC Pross,使用内源性原卟啉IX的光动力学疗法:基本原理和现有临床经验(Photodynamic therapy with endogeneous protoprophyrin IX:basicprinciples and present clinical experience),J.Photochem.,Photobiol.B:Biol.,6(1990)143-148
发明内容
本发明的课题在于提供一种非侵袭性、几乎没有副作用和患者肉体上的痛苦、能安全且简便地治疗过敏性鼻炎的治疗剂。
采用ALA-PDT的癌症治疗正受到广泛的研究,本发明人等也进行了多年的认真研究。虽然已知采用ALA-PDT的癌症治疗是利用在癌细胞中产生·聚集比正常细胞更多的PpIX这一点的疗法,但对于在癌细胞中产生·聚集大量的PpIX的详细机理尚不清楚。另外,对于ALA是否也会聚集在癌细胞、癌组织以外,也尚属未知。本发明人等包罗性地研究了ALA-PDT在所有疾病治疗中的可能性,在其过程中,偶然对过敏性鼻炎也试着进行了研究。本发明人试着对由花粉症导致的过敏性鼻炎患者经口给予ALA,结果发现,PpIX蓄积在鼻粘膜炎症部位。于是,对该PpIX蓄积部位进行了PDT,结果确认到有过敏性鼻炎的治疗效果。进而,该过敏性鼻炎的治疗效果不仅在ALA经口给药时可以确认到,在经皮给药、即以溶液的形式涂布时也可以确认到。本发明是基于这些发现而完成的发明。
即,本发明涉及如下内容:
(1)过敏性鼻炎的治疗剂,其含有5-氨基乙酰丙酸(ALA)或其衍生物或者它们的盐作为有效成分,在照射400nm~700nm的波长的光的5-氨基乙酰丙酸-光动力学疗法(ALA-PDT)中使用;
(2)如上述(1)所述的过敏性鼻炎的治疗剂,其特征在于,照射625nm~640nm的波长的光;
(3)如上述(1)或(2)所述的过敏性鼻炎的治疗剂,其特征在于,经口给药;
(4)如上述(1)或(2)所述的过敏性鼻炎的治疗剂,其特征在于,向鼻腔内经皮给药;
(5)如上述(4)所述的过敏性鼻炎的治疗剂,其特征在于,经皮给药采用涂布的溶液型、水溶性软膏溶解型或胶冻剂溶解型。
另外,作为本发明的实施方式,可例举:
[1]通过ALA-PDT来治疗过敏性鼻炎的方法,其中,给予ALA类,向鼻腔内照射400nm~700nm的波长的光;
[2]如上述[1]所述的治疗过敏性鼻炎的方法,其特征在于,照射625nm~640nm的波长的光;
[3]用于治疗过敏性鼻炎而使用ALA类的方法,其中,通过ALA-PDT治疗过敏性鼻炎,在所述ALA-PDT中向鼻腔内照射400nm~700nm的波长的光;
[4]如上述[3]所述的用于治疗过敏性鼻炎而使用ALA类的方法,其特征在于,照射625nm~640nm的波长的光;
[5]ALA类在用于制备通过ALA-PDT来治疗过敏性鼻炎的药剂中的应用,其特征在于,在所述ALA-PDT中向鼻腔内照射400nm~700nm的波长的光;
[6]如上述[5]所述的ALA类在用于制备治疗过敏性鼻炎的药剂中的应用,其特征在于,照射625nm~640nm的波长的光;
[7]过敏性鼻炎的治疗系统,其用于依次包括以下步骤的过敏性鼻炎的治疗:(a)给予ALA类的ALA给药步骤,(b)照射380nm~420nm的波长的激发光、检测红色的荧光、从而判定PpIX蓄积部位的ALA-PDD步骤,(c)对PpIX蓄积部位照射400nm~700nm的波长的光的ALA-PDT步骤,所述过敏性鼻炎的治疗系统具备ALA-PDD设备及ALA-PDT设备、或者具备ALA-PDT设备;
[8]如上述[7]所述的过敏性鼻炎的治疗系统,其特征在于,ALA-PDT步骤中照射625nm~640nm的波长的光。
如果使用本发明的过敏性鼻炎的治疗剂,则能非侵袭性、几乎没有副作用和患者肉体上的痛苦、安全且简便地治疗过敏性鼻炎。另外,由于过敏性鼻炎的治疗效果至少可持续一年,因此对患者的负担小。
附图说明
图1是表示通过使用支气管镜(PENTAX SAFE-3000)的ALA-PDD确认了鼻粘膜炎症部位的PpIX的蓄积的结果的图。左侧所示为普通照明下的图像,右侧所示为408nm的波长的紫色光下的PpIX荧光图像。
图2是表示PDT用LED照射探针(φ7mm丙烯酸杆导光)的图。
图3是表示使用PDT用LED照射探针(φ7mm丙烯酸杆导光)进行PDT的情况的图。
具体实施方式
作为本发明的过敏性鼻炎的治疗剂,只要是含有由ALA或其衍生物或其盐构成的ALA类作为有效成分、能够在照射400nm~700nm、优选625nm~640nm的波长的光的ALA-PDT中使用的、ALA-PDT用的治疗剂即可,无特别限制,也可以是在ALA-PDT(照射400nm~700nm、优选625nm~640nm的波长的光)之前进行ALA-PDD(照射380nm~420nm的波长的激发光,检测出发射610nm~750nm的波长的光的PpIX蓄积部位)的治疗剂,但特别优选例举无需进行该ALA-PDD的治疗剂。另外,作为使用本发明的过敏性鼻炎的治疗剂的治疗系统,只要是具备ALA-PDT设备的系统即可,无特别限制,也可以具备ALA类的给药设备或ALA-PDD。
ALA或其衍生物如下式(I)所示(式中,R1表示氢原子或酰基,R2表示氢原子、直链或支链状烷基、环烷基、芳基或芳烷基)。
ALA类中,可以优选例举式(I)的R1及R2均为氢原子时的ALA或其盐。ALA是也被称为δ-氨基乙酰丙酸的氨基酸的一种。另外,作为ALA衍生物,可例举式(I)的R1为氢原子或酰基、式(I)的R2为氢原子、直链或支链状烷基、环烷基、芳基或芳烷基的、5-ALA以外的化合物。
作为式(I)中的酰基,可例举甲酰基、乙酰基、丙酰基、丁酰基、异丁酰基、戊酰基、异戊酰基、新戊酰基、己酰基、辛酰基、苄基羰基等直链或支链状的碳原子数1~8的烷酰基、苯甲酰基、1-萘酰基、2-萘酰基等碳原子数7~14的芳酰基。
作为式(I)中的烷基,可例举甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、戊基、异戊基、新戊基、己基、庚基、辛基等直链或支链状的碳原子数1~8的烷基。
作为式(I)中的环烷基,可例举环丙基、环丁基、环戊基、环己基、环庚基、环辛基、环十二烷基、1-环己烯基等饱和或可以存在一部分不饱和键的碳原子数3~8的环烷基。
作为式(I)中的芳基,可例举苯基、萘基、蒽基、菲基等碳原子数6~14的芳基。
作为式(I)中的芳烷基,芳基部分可例举与上述芳基相同的例子,烷基部分可例举与上述烷基相同的例子,具体可例举苄基、苯乙基、苯丙基、苯丁基、二苯甲基(benzhydryl)、三苯甲基、萘甲基、萘乙基等碳原子数7~15的芳烷基。
作为上述ALA衍生物,优选R1为甲酰基、乙酰基、丙酰基、丁酰基等的化合物、上述R2为甲基、乙基、丙基、丁基、戊基等的化合物,可以优选例举上述R1和R2的组合为甲酰基和甲基、乙酰基和甲基、丙酰基和甲基、丁酰基和甲基、甲酰基和乙基、乙酰基和乙基、丙酰基和乙基、丁酰基和乙基的组合等。
ALA类只要在机体内以式(I)的ALA或其衍生物的状态作为有效成分起作用即可,根据给药的方式,可以制成用于提高溶解性的各种盐、酯或被机体内的酶分解的前药(前体)来给药。例如,作为ALA及其衍生物的盐,可例举药理学上可接受的酸加成盐、金属盐、铵盐、有机胺加成盐等。作为酸加成盐,可举出例如盐酸盐、氢溴酸盐、氢碘酸盐、磷酸盐、硝酸盐、硫酸盐等各无机酸盐、甲酸盐、乙酸盐、丙酸盐、甲苯磺酸盐、琥珀酸盐、草酸盐、乳酸盐、酒石酸盐、乙醇酸盐、甲磺酸盐、丁酸盐、戊酸盐、柠檬酸盐、富马酸盐、马来酸盐、苹果酸盐等各有机酸加成盐。作为金属盐,可例举锂盐、钠盐、钾盐等各碱金属盐、镁、钙盐等各碱土金属盐、铝、锌等各金属盐。作为铵盐,可例举铵盐、四甲基铵盐等烷基铵盐等。作为有机胺盐,可例举三乙胺盐、哌啶盐、吗啉盐、甲苯胺盐等各盐。需要说明的是,这些盐在使用时也可以制成溶液来使用。
以上ALA类中,优选的是ALA及ALA甲酯、ALA乙酯、ALA丙酯、ALA丁酯、ALA戊酯等各种酯类以及它们的盐酸盐、磷酸盐、硫酸盐,可以特别优选例举ALA盐酸盐、ALA磷酸盐。
上述ALA类可以通过化学合成、利用微生物的生产、利用酶的生产中的任一种公知的方法来制造。另外,上述ALA类可以形成水合物或溶剂化物,并且可以将任意一种单独使用或将两种以上适当组合使用。
将上述ALA类调制成水溶液的情况下,为了防止ALA类的分解,需要注意不要让水溶液呈碱性。呈碱性的情况下,可以通过除去氧来防止分解。
上述ALA-PDT是用于治疗过敏性鼻炎的方法,该治疗利用以下原理:给予对光反应的化合物、进行通过照射光来治疗靶部位的PDT时,给予其本身不具有光增敏作用的ALA类,经由色素生物合成通路而衍生出的PpIX特异性地聚集在鼻粘膜炎症部位的细胞内,使蓄积在鼻粘膜炎症细胞内的PpIX激发,从而将周围的氧分子光激发,其结果,生成的单线态氧由于其强大的氧化力而具有杀细胞效果;作为上述使PpIX激发的光的波长,只要是红色光的波长即可,具体可例举400nm~700nm、优选625nm~640nm,其中优选635nm。
对于上述不一定要实施、可以任意实施的ALA-PDD,是在本发明的ALA-PDT之前、利用对蓄积在鼻粘膜炎症细胞内的PpIX照射紫色光时会发出红色的荧光这一点来确定鼻粘膜炎症部位的判定方法,作为上述紫色光的波长,只要至少在380nm~420nm的范围内即可,可举出例如400~420nm、403~410nm等,其中优选408nm。
作为本发明的治疗剂中的ALA类的给药方法,可例举也包括舌下给药在内的经口给药、包括静脉滴注在内的静脉注射、采用巴布膏剂、栓剂、涂布的溶液型等进行的经皮给药,其中优选经口给药、向鼻腔内的经皮给药,如果从效率性及简便性的观点来考虑,则可以优选例举涂布于鼻粘膜炎症部位的经皮给药。经口给药的情况下,在炎症部位积存大量的PpIX,但也会被正常粘膜摄取,因此例如感受气味的嗅觉细胞可能会因为光照射而受到损伤,而用溶解液等局部给药的情况下,可以使PpIX不被位于鼻腔内深处上部的嗅觉细胞摄取,因此可避免嗅觉损伤等副作用。作为经口给药剂型的治疗剂的剂型,可例举粉末、颗粒、片剂、胶囊剂、糖浆剂、悬浊液等,作为静脉注射剂型的治疗剂,可例举注射剂、滴剂等。另外,作为向鼻腔内的经皮给药型的治疗剂的剂型,可例举溶液型、水溶性软膏溶解型、胶冻剂溶解型、喷雾型等。例如,作为通过涂布的溶液型进行经皮给药的方法,具体可例举使充分含有ALA类溶液的纱布、脱脂棉等液体保持材料与鼻腔内的鼻粘膜炎症部位接触的方法。作为ALA类的给药量,只要PpIX在鼻粘膜炎症部位的聚集量是ALA-PDT的有效量即可,作为具体的ALA类的给药量,例如经口给药的情况下,以ALA换算每1kg体重为1mg~1000mg,优选为5mg~100mg,更优选为10mg~30mg,进一步更优选为15mg~25mg,通过涂布的溶液型进行经皮给药的情况下,ALA类溶液的浓度以ALA换算为1重量%~90重量%,优选为2重量%~40重量%,更优选为3重量%~10重量%,进一步更优选为4重量%~6重量%。另外,以溶液的形态使用ALA类的情况下,为了防止ALA类的分解,优选在调制时注意不要让水溶液呈碱性。呈碱性的情况下,可以通过除去氧来防止有效成分的分解。
本发明的治疗剂可以根据需要添加其它药效成分、营养剂、载体等其它任意成分。作为任意成分,例如可以添加结晶纤维素、明胶、乳糖、淀粉、硬脂酸镁、滑石、植物性及动物性脂肪、油脂、橡胶、聚亚烷基二醇等药学上可接受的常规的载体、粘结剂、稳定剂、溶剂、分散介质、增量剂、赋形剂、稀释剂、pH缓冲剂、崩解剂、增溶剂、助溶剂、等渗剂等各种制剂用配合成分。
上述ALA-PDT步骤中,使用ALA-PDT设备,其能对要照射的鼻粘膜炎症部位的范围照射红色光、具体而言照射具有400nm~700nm的波长、优选625nm~640nm的波长、更优选635nm的波长的光。作为照射上述光的光源,可使用公知的光源,可举出例如红色LED(发光二极管)、红色半导体激光器、具有强红色发光光谱的放电灯等,因为在装置紧凑、成本及可搬运性方面有利,所以可以优选例举红色LED。另外,以红色半导体激光器作为光源的情况下,激光的功率密度优选为20mW/cm2~400mW/cm2,能量密度优选为25J/cm2~100J/cm2。激光既可以是连续光,也可以是脉冲光,通过使用脉冲光,可减小对正常的皮肤表面的损伤,从这一方面考虑更优选脉冲光。作为具体的照射方法,可例举一边用能进行荧光观察的支气管镜来观察鼻粘膜炎症部位、一边以例如100J/cm2的能量密度进行照射的方法,对鼻粘膜炎症部位进行照射时的照射直径优选为10mm以上,为15mm以上时,对患部的照射时间缩短,故优选。
如上所述,使用本发明的治疗剂的治疗方法的特征之一为,无需在ALA-PDT之前进行ALA-PDD,简便,但也可以进行ALA-PDD。作为该ALA-PDD步骤中使用的ALA-PDD设备,可例举PpIX的激发光照射设备、激发状态的PpIX特有的红色荧光检测设备或由它们一体化而得的设备。作为从PpIX的激发光照射设备照射的光,优选能通过使PpIX激发来观察PpIX特有的红色荧光的波长的光,只要是与属于PpIX的吸收峰(属于所谓的索雷谱带(Soretband))的紫外光相近的紫色的波长的光、至少是380nm~420nm的范围内的波长的光即可,可举出例如400~420nm、403~410nm等,其中优选408nm。
作为上述ALA-PDD步骤中照射激发光的光源,可使用公知的光源,可举出例如紫色LED,优选闪光型紫色LED、半导体激光器等光源,可例举在装置紧凑、成本及可搬运性方面有利的紫色LED,其中可以优选闪光型紫色LED、紫色半导体二极管。另外,作为用于检测PpIX蓄积部位、判断要照射的鼻粘膜炎症部位的范围的、用于检测红色的荧光(具体是610nm~750nm、优选625~638nm的波长的荧光)的红色荧光检测设备,可例举采用肉眼的检测设备、采用CCD照相机的检测设备。
作为将激发光照射设备和红色荧光检测设备一体化的ALA-PDD设备,可例举光源·计测用细径光纤,作为在使蓄积的PpIX激发的ALA-PDD步骤中照射的激发光的光源,优选为了对于微小的鼻粘膜炎症部位也能进行PpIX的检测而放射照度强、为了能进行精确的自动识别而照射面积狭窄的半导体激光器光源,优选具有引导激发光从一端向外部出射的激发光导光部,作为激发光导光部,具体可例举细径光纤。作为光源中使用的元件,可使用InGaN等半导体混晶,通过改变InGaN的配比,可以发出紫色光。具体而言,可以优选例举直径5.6mm左右的紧凑的激光二极管。可例举与台式PC相当的尺寸的装置,该装置由从激光二极管输出4束激光的端口和光谱测定用的端口通过内置式高灵敏度分光镜连接而成。另外,在接收被上述激发光激发的PpIX所发出的荧光的受光工序中使用计测用细径光纤,该计测用细径光纤和上述光源用细径光纤一体化,将接收的荧光引导至检测器,进行PpIX蓄积部位的判定。
以下例举实施例等对本发明进行具体说明,但本发明的技术范围不限定于这些实施例等。
实施例1
[采用ALA经口给药的过敏性鼻炎的治疗]
对3名过敏性鼻炎的受试志愿者经口给予20mg/kg的ALA盐酸盐,约6小时后用能进行荧光观察的支气管镜(PENTAX社制SAFE-3000)对鼻腔照射408nm的紫色光,进行ALA-PDD。其结果,检测出摄取了PpIX的鼻粘膜炎症部位,为红色荧光(图1)。对该鼻粘膜炎症部位照射具有635nm的波长的红色LED(发光二极管(LightEmitting Diode))(图2)的光,直至用肉眼无法观察到红色荧光为止(图3)。更具体而言,照射一定时间的具有635nm的波长的红色LED光后,中断该PDT照射,更换照射装置,将支气管镜(PENTAX社制SAFE-3000)插入鼻腔内,观察红色光后,再次进行PDT照射。其结果,虽然直到照射后数日为止都能在3名受试者中确认到强烈的鼻涕、打喷嚏的症状,但上述症状在随后的数周内减轻。这些结果表明,蓄积在发生炎症的鼻粘膜中的PpIX被激发,生成活性氧,结果该活性氧使鼻粘膜上皮变性,从而引起过敏反应性的降低。
已知PpIX局部地蓄积在鼻粘膜炎症部位,但为了再次确认能够实施简便的ALA-PDT,对整个鼻腔内照射红色半导体激光的红色光,从而验证能否治疗过敏性鼻炎。对7名成年男性及5名成年女性共计12名花粉症的受试者经口给予20mg/kg的ALA盐酸盐,6小时后对鼻腔内照射6分钟的具有635nm的波长的红色半导体激光100J。其结果,12人的由花粉症导致的强烈的鼻涕、打喷嚏的症状消失(3名)或减轻(5名),该效果至少在照射后持续1年。该结果表明,即使不特定鼻粘膜炎症部位,也能治疗过敏性鼻炎。
实施例2
[采用ALA经皮给药的过敏性鼻炎的治疗]
接下来,对给予的ALA盐酸盐即使是涂布的液体型是否也能治疗过敏性鼻炎进行研究。对4名成年男性花粉症受试者,用充分浸有5重量%ALA盐酸盐生理盐水溶解液的棉花涂布鼻腔内,留置1小时后除去该浸渍棉花。对3名受试者在除去浸渍棉花后立即向鼻腔内照射6分钟的具有635nm的波长的红色半导体激光100J,对于剩下的1名受试者,在除去浸渍棉花1小时后向鼻腔内照射6分钟的具有635nm的波长的红色半导体激光100J。其结果,4人的由花粉症导致的强烈的鼻涕、打喷嚏的症状,在1小时后进行照射的1人中消失,在立即进行照射的3人中得到减轻。该结果表明,给予的ALA盐酸盐即使是涂布的液体型也能治疗过敏性鼻炎。进而,对于通过涂布该液体型进行的治疗,通过将ALA盐酸盐溶液直接涂布于鼻粘膜炎症部位周边,与经口给药相比能够将给予的ALA盐酸盐的量抑制在较低水平,另外,PpIX在短时间内蓄积在鼻粘膜炎症部位,因此如果从费用/效果、时间/效果的观点考虑,是比经口给药更好的治疗。
Claims (5)
1.过敏性鼻炎的治疗剂,其含有5-氨基乙酰丙酸(ALA)或其衍生物或者它们的盐作为有效成分,在照射400nm~700nm的波长的光的5-氨基乙酰丙酸-光动力学疗法(ALA-PDT)中使用。
2.如权利要求1所述的过敏性鼻炎的治疗剂,其特征在于,照射625nm~640nm的波长的光。
3.如权利要求1或2所述的过敏性鼻炎的治疗剂,其特征在于,经口给药。
4.如权利要求1或2所述的过敏性鼻炎的治疗剂,其特征在于,向鼻腔内经皮给药。
5.如权利要求4所述的过敏性鼻炎的治疗剂,其特征在于,经皮给药采用涂布的溶液型、水溶性软膏溶解型或胶冻剂溶解型。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011-134489 | 2011-06-16 | ||
JP2011134489 | 2011-06-16 | ||
PCT/JP2012/003945 WO2012172821A1 (ja) | 2011-06-16 | 2012-06-15 | アレルギー性鼻炎の治療剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103717215A true CN103717215A (zh) | 2014-04-09 |
CN103717215B CN103717215B (zh) | 2016-08-17 |
Family
ID=47356823
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201280028688.3A Expired - Fee Related CN103717215B (zh) | 2011-06-16 | 2012-06-15 | 过敏性鼻炎的治疗剂 |
Country Status (6)
Country | Link |
---|---|
US (1) | US9550073B2 (zh) |
EP (1) | EP2722041B1 (zh) |
JP (1) | JP5713473B2 (zh) |
CN (1) | CN103717215B (zh) |
HK (1) | HK1193053A1 (zh) |
WO (1) | WO2012172821A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108434100A (zh) * | 2018-04-27 | 2018-08-24 | 中南大学湘雅三医院 | 一种用于光动力疗法治疗鼻咽喉腔疾病的喷雾光敏剂组合物 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103930103B (zh) | 2011-10-12 | 2016-08-24 | 思佰益药业股份有限公司 | 移植器官的成活促进剂 |
HUE043511T2 (hu) * | 2012-07-13 | 2019-08-28 | Sbi Pharmaceuticals Co Ltd | Immuntoleranciát kiváltó szer |
CN116617586B (zh) * | 2023-05-25 | 2024-01-23 | 北京工业大学 | 一种紫外光交联辅助红外光照射的光调控系统及应用和方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1533271A (zh) * | 2001-07-26 | 2004-09-29 | �Ƹ��� | 在光化疗法中作为光敏化剂的5-氨基乙酰丙酸及其酯与另一光敏剂的组合,以及它们在治疗创伤中的用途 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5234940A (en) * | 1989-07-28 | 1993-08-10 | Queen's University | Photochemotherapeutic method using 5-aminolevulinic acid and precursors thereof |
US5079262A (en) | 1989-07-28 | 1992-01-07 | Queen's University At Kingston | Method of detection and treatment of malignant and non-malignant lesions utilizing 5-aminolevulinic acid |
CA2461070C (en) * | 1992-04-08 | 2007-12-18 | Queen's University At Kingston | Photochemotherapeutic method using precursors of protoporphyrin ix |
US6520384B2 (en) * | 2001-04-30 | 2003-02-18 | Ketan C. Mehta | Apparatus and method for nasal rinse |
ATE493382T1 (de) * | 2004-03-30 | 2011-01-15 | Cosmo Oil Co Ltd | 5-aminolevulinsäure-phosphatsalz, verfahren zu dessen herstellung und dessen verwendung |
KR100966318B1 (ko) * | 2004-09-02 | 2010-06-28 | 코스모세키유 가부시키가이샤 | 건강 기능 향상제 |
JP5034032B2 (ja) | 2004-09-29 | 2012-09-26 | Sbiファーマ株式会社 | 腫瘍診断剤 |
JP5098051B2 (ja) * | 2007-04-05 | 2012-12-12 | Sbiファーマ株式会社 | ミトコンドリア障害脳疾患治療剤及び診断剤 |
ES2822122T3 (es) * | 2008-04-22 | 2021-04-29 | Sbi Pharmaceuticals Co Ltd | Método de detección del cáncer de vejiga |
EP2340821B1 (en) * | 2008-10-27 | 2017-01-25 | SBI Pharmaceuticals Co., Ltd. | Prophylactic/ameliorating agent for adult diseases comprising 5-aminolevulinic acid, derivative of 5-aminolevulinic acid, or salt of 5-aminolevulinic acid or the derivative of 5-aminolevulinic acid as active ingredient |
JP5611548B2 (ja) * | 2009-07-08 | 2014-10-22 | Sbiファーマ株式会社 | 5−アミノレブリン酸若しくはその誘導体、又はそれらの塩を有効成分とするがんの予防・改善剤 |
CN102905702A (zh) * | 2010-05-19 | 2013-01-30 | 思佰益药业股份有限公司 | 以5-氨基乙酰丙酸或其衍生物作为有效成分的抗疟药 |
JP5522421B2 (ja) * | 2010-09-14 | 2014-06-18 | 学校法人東京農業大学 | がん温熱療法の作用増強剤 |
-
2012
- 2012-06-15 EP EP12801049.3A patent/EP2722041B1/en active Active
- 2012-06-15 US US14/125,744 patent/US9550073B2/en active Active
- 2012-06-15 WO PCT/JP2012/003945 patent/WO2012172821A1/ja active Application Filing
- 2012-06-15 CN CN201280028688.3A patent/CN103717215B/zh not_active Expired - Fee Related
- 2012-06-15 JP JP2013520445A patent/JP5713473B2/ja active Active
-
2014
- 2014-07-03 HK HK14106736.0A patent/HK1193053A1/zh not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1533271A (zh) * | 2001-07-26 | 2004-09-29 | �Ƹ��� | 在光化疗法中作为光敏化剂的5-氨基乙酰丙酸及其酯与另一光敏剂的组合,以及它们在治疗创伤中的用途 |
Non-Patent Citations (2)
Title |
---|
N.H.BEXFIELD,ET AL.: "Photodynamic Therapy of Superficial Nasal Planum Squamous Cell Carcinomas in Cats: 55 Cases", 《J VET INTERN MED》, vol. 22, 31 December 2008 (2008-12-31), pages 1385 - 1389, XP055143355, DOI: 10.1111/j.1939-1676.2008.0186.x * |
ZSANETT CSOMA,ET AL.: "PUVA treatment of the nasal cavity improves the clinical symptoms of allergic rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin", 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY》, vol. 83, 10 January 2006 (2006-01-10), pages 21 - 26 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108434100A (zh) * | 2018-04-27 | 2018-08-24 | 中南大学湘雅三医院 | 一种用于光动力疗法治疗鼻咽喉腔疾病的喷雾光敏剂组合物 |
Also Published As
Publication number | Publication date |
---|---|
CN103717215B (zh) | 2016-08-17 |
HK1193053A1 (zh) | 2014-09-12 |
JP5713473B2 (ja) | 2015-05-07 |
EP2722041A1 (en) | 2014-04-23 |
EP2722041B1 (en) | 2018-10-24 |
JPWO2012172821A1 (ja) | 2015-02-23 |
WO2012172821A1 (ja) | 2012-12-20 |
US20140188034A1 (en) | 2014-07-03 |
EP2722041A4 (en) | 2014-11-05 |
US9550073B2 (en) | 2017-01-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5827702B2 (ja) | アミノレブリン酸およびその誘導体の使用 | |
CN1137087C (zh) | 用作光化学疗法中的光致敏剂的5-氨基酮戊酸的酯 | |
ES2639021T3 (es) | Sales de adición de ácido del ácido 5-aminolevulínico o sus derivados | |
US7348361B2 (en) | Solution for diagnosing or treating tissue pathologies | |
BR112012003283B1 (pt) | Sal farmaceuticamente aceitável de um agente fotossensibilizante anfifílico, composição farmacêutica, kit para uso em um método de internalização fotoquímica e uso de um sal farmaceuticamente aceitável de um agente fotossensibilizante anfifílico | |
NO327985B1 (no) | Gule 5-aminolevulinsyrekrystaller, steril losning av disse, steril pakke som inneholder dem, fremgangsmate for fremstilling av og forbedring av krystallene, sett som omfatter krystallene og anvendelse av dem for fremstilling av medikament | |
CN103717215A (zh) | 过敏性鼻炎的治疗剂 | |
EP2272538B1 (en) | Method of detecting bladder cancer | |
JP2011001307A (ja) | 5−アミノレブリン酸による子宮頸がん判定・治療システム | |
JP5883889B2 (ja) | 光線力学的診断剤、及び、フォトブリーチング防止剤 | |
CN110520160B (zh) | Ala-pdt或ala-pdd中的光动力学效应的增强剂 | |
KR101308507B1 (ko) | 트립토판을 함유하는 여드름 치료제 및 피지분비 억제제, 및 이를 포함하는 광역학적 치료용 키트 | |
US20030087947A1 (en) | Novel photosensitizers of 9-hydroxypheophorbide-a derivatives used for photodynamic therapy | |
WO2020066577A1 (ja) | 歯周病治療薬 | |
RU2455039C1 (ru) | Способ фотодинамической терапии злокачественных новообразований | |
RU2191010C2 (ru) | Сложные эфиры 5-аминолевулиновой кислоты в качестве фотосенсибилизаторов в фотохимиотерапии | |
RomiszewskA et al. | The use of 5-aminolevulinic acid and its derivatives in photodynamic therapy and diagnosis | |
WO2021070896A1 (ja) | 口臭改善剤又は口臭予防剤 | |
JP2011026221A (ja) | プロトポルフィリンix細胞内集積増強組成物 | |
JP2008303197A (ja) | 細胞内プロトポルフィリンix集積量増加剤及びそれを含有した光線力学的診断用又は治療用組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1193053 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1193053 Country of ref document: HK |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160817 |