JPS62207226A - Pharmaceutical for nasotracheal administration - Google Patents
Pharmaceutical for nasotracheal administrationInfo
- Publication number
- JPS62207226A JPS62207226A JP61050896A JP5089686A JPS62207226A JP S62207226 A JPS62207226 A JP S62207226A JP 61050896 A JP61050896 A JP 61050896A JP 5089686 A JP5089686 A JP 5089686A JP S62207226 A JPS62207226 A JP S62207226A
- Authority
- JP
- Japan
- Prior art keywords
- administration
- active substance
- surfactant
- physiologically active
- pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000013543 active substance Substances 0.000 claims abstract description 15
- 239000004094 surface-active agent Substances 0.000 claims abstract description 12
- 102000014150 Interferons Human genes 0.000 claims abstract description 8
- 108010050904 Interferons Proteins 0.000 claims abstract description 8
- 229940079322 interferon Drugs 0.000 claims abstract description 8
- 229930182490 saponin Natural products 0.000 claims abstract description 5
- 150000007949 saponins Chemical class 0.000 claims abstract description 5
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 4
- 102000006992 Interferon-alpha Human genes 0.000 claims description 9
- 108010047761 Interferon-alpha Proteins 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 6
- 230000002519 immonomodulatory effect Effects 0.000 claims description 6
- 239000003833 bile salt Substances 0.000 claims description 3
- 125000002345 steroid group Chemical group 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 abstract description 11
- 239000007924 injection Substances 0.000 abstract description 6
- 238000002347 injection Methods 0.000 abstract description 6
- 150000003431 steroids Chemical group 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 210000003928 nasal cavity Anatomy 0.000 abstract description 3
- 239000007900 aqueous suspension Substances 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract description 2
- 239000000843 powder Substances 0.000 abstract description 2
- 230000001900 immune effect Effects 0.000 abstract 3
- 230000001105 regulatory effect Effects 0.000 abstract 3
- 125000003523 triterpene group Chemical group 0.000 abstract 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 7
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 108010063738 Interleukins Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 229940093761 bile salts Drugs 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- -1 methylpentose Chemical compound 0.000 description 2
- HFWWEMPLBCKNNM-UHFFFAOYSA-N n-[bis(hydroxyamino)methyl]hydroxylamine Chemical compound ONC(NO)NO HFWWEMPLBCKNNM-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical class C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010007979 Glycocholic Acid Chemical class 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108010048043 Macrophage Migration-Inhibitory Factors Proteins 0.000 description 1
- 102100037791 Macrophage migration inhibitory factor Human genes 0.000 description 1
- RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Chemical class OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Chemical class OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical class C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- 229940099347 glycocholic acid Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical class C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は免疫調節作用を有する生理活性物質およびステ
ロイド骨格またはトリテルベン骨格を持つ界面活性剤を
含有する経鼻投与製剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a nasal preparation containing a physiologically active substance having an immunomodulatory effect and a surfactant having a steroid skeleton or a triterbene skeleton.
免疫調節作用を有する生理活性物質としては主にペプチ
ド、蛋白質あるいは糖蛋白質などが知られているがこれ
らの投与は従来、主として注射剤に限られていた。しか
しながら、注射暴による投与は苦痛を伴い、不便である
ため、注射投与以外の筒便な方法によって投与されるこ
とが望まれている。Peptides, proteins, glycoproteins, and the like are mainly known as physiologically active substances having immunomodulatory effects, but their administration has heretofore been mainly limited to injections. However, since administration by injection is painful and inconvenient, it is desired to administer by a more convenient method other than injection administration.
本発明者らは、このような観点から免疫調節作用を有す
る生理活性物質を安全にかつ頻回に投与できるように、
経鼻投与製剤について、鋭意検討した結果、ステロイド
骨格またはトリテルベン骨格を持つ界面活性剤を添加す
ることにより生理活性物質が鼻腔粘膜から速やかに吸収
されることを見出し、本発明を完成した。From this perspective, the present inventors have developed a method for safely and frequently administering physiologically active substances that have immunomodulatory effects.
As a result of extensive research into nasal formulations, the inventors discovered that by adding a surfactant having a steroid skeleton or a triterbene skeleton, physiologically active substances can be rapidly absorbed through the nasal mucosa, and have completed the present invention.
免疫調節作用を有する生理活性物質としては例えばイン
ターフェロン（ＩＦＮ）、インターロイキン（ＩＬ）、
コロニー刺激因子（Ｃ３Ｆ）、マクロファージ活性化因
子（ＭＡＦ）、マクロファージ遊走阻止因子（ＭＩＦ）
、腫瘍壊死因子（ＴＮＦ）ばか各種サイトカイン類など
が挙げられる。なお、ここで言うインターフェロンとは
α、β、Ｔその他いずれのインターフェロンでもよくま
たそれらの組み合わせでもよいことはもちろんである。Examples of physiologically active substances having immunomodulatory effects include interferon (IFN), interleukin (IL),
Colony stimulating factor (C3F), macrophage activating factor (MAF), macrophage migration inhibitory factor (MIF)
, tumor necrosis factor (TNF) and various cytokines. It should be noted that the interferon referred to herein may of course be any interferon such as α, β, T, or any other type of interferon, or a combination thereof.
同様にインターロイキンはＩＬ−１、！Ｌ−２あるいは
ＩＬ−３その他いずれでもよく、コロニー刺激因子は多
能性Ｃ３Ｆ（ｍｕｌｔｉ −Ｃ３Ｆ） 、顆粒球−単球
マクロファージＣ３Ｆ （ＧＭ−Ｃ３Ｆ＞ 、顆粒球−
Ｃ５Ｆ（Ｇ−Ｃ３Ｆ）または単球マクロファージＣ３Ｆ
（Ｍ−Ｃ３Ｆ）その他いずれのＣ３Ｆでもよく、また
これらの混合物でもよい、ＭＡＦおよびＭＩＦについて
も、今後の研究により精製、分離が期待される各サブク
ラスはそれぞれ同様の分子量をもつ糖蛋白質または蛋白
質であると予想され、本発明の適用によりいずれも経鼻
投与が可能であると考えられる。Similarly, interleukin is IL-1! L-2 or IL-3 or any other may be used, and the colony stimulating factor may be multi-C3F, granulocyte-monocyte-macrophage C3F (GM-C3F>, granulocyte-monocyte-macrophage C3F), etc.
C5F (G-C3F) or monocyte-macrophage C3F
(M-C3F) Any other C3F or a mixture of these may be used. Regarding MAF and MIF, each subclass that is expected to be purified and separated through future research is a glycoprotein or protein with a similar molecular weight. It is expected that there will be some, and it is thought that nasal administration of any of them will be possible by application of the present invention.
また本発明に用いる生理活性物質はその製法によらず、
生体からの抽出物質、人工合成物質また遺伝子組み換え
法によって得られたものでもいずれでもよい、また本発
明における生理活性物質はそれ自身を用いてもよく、ま
た、それぞれの薬物に適当な安定化剤、緩衝剤等を含ん
でいるような市販のものを用いてもよい。In addition, the physiologically active substance used in the present invention does not depend on its manufacturing method,
The physiologically active substances in the present invention may be extracted from living organisms, artificially synthesized substances, or obtained by genetic recombination methods.The physiologically active substances in the present invention may be used on their own, and stabilizers suitable for each drug may be used. A commercially available one containing a buffering agent or the like may also be used.
経鼻投与とは鼻腔粘膜から薬物を吸収せしめようとする
投与形態であり、具体的には例えば水溶液を鼻腔粘膜に
噴霧することにより行われる。したがって、本発明の製
剤の形態は鼻腔内にスプレーできるように液剤であるこ
とが便利であるが、保存安定性の面から凍結乾燥粉末と
し、用時溶解液に溶解して使用してもよい、その他、懸
濁液、ゲルまたは粉末でもよく特に限定されない。Nasal administration is a form of administration in which the drug is absorbed through the nasal mucosa, and is specifically carried out, for example, by spraying an aqueous solution onto the nasal mucosa. Therefore, it is convenient for the formulation of the present invention to be in the form of a liquid so that it can be sprayed into the nasal cavity, but from the viewpoint of storage stability, it may also be made into a lyophilized powder and dissolved in a solution before use. In addition, it may be a suspension, gel, or powder without particular limitation.
界面活性剤は天然から得られるものであっても人工合成
によって得られるものでもよいが、ステロイド骨格また
はトリテルベン骨格を持つ化合物が好ましく、例えば、
サポニン、胆汁酸塩、あるいはスクアレンなどが挙げら
れる。The surfactant may be obtained from nature or by artificial synthesis, but compounds having a steroid skeleton or triterbene skeleton are preferable, for example,
Examples include saponins, bile salts, and squalene.
サポニンはステロイドあるいはトリテルペノイドを非糖
部とするオリゴ配糖体であり、糖成分はグルコース、ガ
ラクトース、ペントース、メチルペントース、アラビノ
ース、゛グルクロン酸等が挙げられる。Saponin is an oligoglycoside whose non-sugar moiety is a steroid or triterpenoid, and sugar components include glucose, galactose, pentose, methylpentose, arabinose, and glucuronic acid.
胆汁酸塩は、例えば、コール酸、グリココール酸、タウ
ロコール酸、デオキシコール酸、デヒドロコール酸等の
アルカリ金属塩などが含まれる。Bile salts include, for example, alkali metal salts of cholic acid, glycocholic acid, taurocholic acid, deoxycholic acid, dehydrocholic acid, and the like.
界面活性剤は単独で使用してもよいし、二種類以上を組
み合わせて用いてもよい、製剤に対する界面活性剤の含
量は、例えば、水溶液あるいは懸濁液中において通常０
．旧〜５０Ｗ／■％、より好ましくは０．０１〜３０Ｗ
／Ｖ％である。The surfactant may be used alone or in combination of two or more types.The content of the surfactant in the preparation is usually 0 or 0 in an aqueous solution or suspension.
．． Old ~50W/■%, more preferably 0.01~30W
/V%.
薬物の量はそれぞれの活性成分の種類、活性度、治療目
的により異なり、それぞれに適当な量を選択すればよい
が、例えばインターフェロンαの場合ｌ製剤中に１０’
−１ｏ’ＩＵを含有するように設計されることが好まし
い、このように設計された製剤をその症状や治療目的に
応じて１日１回〜数回適量経鼻的に投与することにより
薬物の吸収が期待でき治療効果を期待することができる
。The amount of drug varies depending on the type, activity, and therapeutic purpose of each active ingredient, and an appropriate amount may be selected for each. For example, in the case of interferon α, 10'
- Preferably designed to contain 10' IU, the drug can be administered nasally in an appropriate amount once to several times a day depending on the symptoms and therapeutic purpose. Absorption is expected and therapeutic effects can be expected.
本発明の製剤は、公知の手段に従って任意の順序で所要
成分を混合、溶解、懸濁あるいは乳化することによって
製造できる０例えば生理活性物質および一種類以上の界
面活性剤を水または経鼻投与用製剤に通常許容される有
機溶媒を含む水溶液（例えばエタノール水溶液等）に溶
解することによって得られる。The formulation of the present invention can be prepared by mixing, dissolving, suspending or emulsifying the required ingredients in any order according to known means. It can be obtained by dissolving it in an aqueous solution (for example, an aqueous ethanol solution) containing an organic solvent that is normally acceptable for pharmaceutical preparations.
こあ際、薬学上許容される緩衝剤、安定化剤、保存剤、
溶解補助剤、ｐ）（調整剤、等張化剤などを必要に応じ
て加えることができる。In this case, pharmaceutically acceptable buffers, stabilizers, preservatives,
A solubilizing agent, p) (adjusting agent, tonicity agent, etc.) can be added as necessary.
さらに凍結乾燥などにより固体状の製剤を得ることも可
能である。Furthermore, it is also possible to obtain a solid preparation by freeze-drying or the like.
以下に実施例および実験例を示すが、本発明がこれらに
限定されるものではない。Examples and experimental examples are shown below, but the present invention is not limited thereto.
実施例１
インターフェロンαを含む水溶液〔ヒト血清アルブミン
、食塩、トリスヒドロキシアミノメタン、グリシンも含
まれている〕 （３×１０’ Ｉ Ｕ／ｍｌ） ５
ｍｌにコール酸ナトリウム１００ ＊を加え、経鼻投与
用製剤を得た。Example 1 Aqueous solution containing interferon α [also contains human serum albumin, salt, trishydroxyaminomethane, and glycine] (3 x 10' I U/ml) 5
ml of sodium cholate was added to obtain a preparation for nasal administration.
実施例２
インターフェロンαを含む水溶液〔ヒト血清アルブミン
、食塩、トリスヒドロキシアミノメタン、グリシンも含
まれている〕 （６×１０’ｌＵ／蒙１） ５ｍｌに
タウロコール酸ナトリウム１００ｍｇを添加した。この
混合液を凍結乾燥し、用時溶解型の経鼻投与用製剤を得
た。Example 2 100 mg of sodium taurocholate was added to 5 ml of an aqueous solution containing interferon α (also containing human serum albumin, salt, trishydroxyaminomethane, and glycine) (6×10'lU/1 month). This liquid mixture was freeze-dried to obtain a preparation for nasal administration that dissolves at the time of use.
実施例３
インターフェロンα水？ａＫ （１５ｘ １０’ｌ Ｕ
／ｍｌ） １ｍｌにグリココール酸ナトリウム１０喀
を添加、溶解し、経鼻投与用水溶液とした。Example 3 Interferon alpha water? aK (15x 10'l U
1 ml of sodium glycocholate was added and dissolved to prepare an aqueous solution for nasal administration.
実施例４
サポニン５０＊をインターフェロンα水溶液（１５Ｘ
１ Ｇ” Ｔ Ｕ／＋＊ｌ） ５端ｌに溶解し、経
鼻投与用水溶液とした。Example 4 Saponin 50* was mixed with interferon α aqueous solution (15X
1 G" T U/+*l) was dissolved in the 5-end l to prepare an aqueous solution for nasal administration.
実験例１
ウィスター系雄性ラット（体重２００〜３００ｇ）をペ
ンドパルビタール腹腔内注射により酔した。実施例３お
よび４で作成した経鼻投与用インターフェロンα製剤を
Ｑ、１ｍｌ／ｋｇの容量で鼻腔内にマイクロピペットで
投与した。Experimental Example 1 Male Wistar rats (body weight 200-300 g) were intoxicated by intraperitoneal injection of pendoparbital. The interferon α preparations for intranasal administration prepared in Examples 3 and 4 were administered into the nasal cavity using a micropipette in a volume of Q, 1 ml/kg.
その後あらかじめ頚静脈に挿入したカニユーレから経時
的に採血を行い、血清中のインターフェロンαの濃度を
ラジオイムノアッセイ（ＲＩＡ）により定量した。Thereafter, blood was collected over time from a cannula previously inserted into the jugular vein, and the concentration of interferon α in the serum was determined by radioimmunoassay (RIA).
なお、比較のために、界面活性剤を含存しないインター
フェロンα水溶液を用いて同様の実験を行った。For comparison, a similar experiment was conducted using an interferon α aqueous solution containing no surfactant.
結果を表１に示す、なお各値はラット３〜５匹の平均値
で示した。The results are shown in Table 1, and each value is the average value of 3 to 5 rats.
Claims (4)
イド骨格またはトリテルベン骨格を持つ界面活性剤を含
有することを特徴とする経鼻投与用製剤。(1) A preparation for nasal administration, which is characterized by containing a physiologically active substance having an immunomodulating effect and a surfactant having a steroid skeleton or a triterbene skeleton.
ェロンである特許請求の範囲第１項記載の経鼻投与用製
剤。(2) The formulation for nasal administration according to claim 1, wherein the physiologically active substance having an immunomodulatory effect is interferon.
許請求の範囲第２項記載の経鼻投与用製剤。(3) The formulation for nasal administration according to claim 2, wherein the interferon is interferon α.
請求の範囲第１項記載の経鼻投与用製剤。(4) The formulation for nasal administration according to claim 1, wherein the surfactant is saponin or bile salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61050896A JPS62207226A (en) | 1986-03-07 | 1986-03-07 | Pharmaceutical for nasotracheal administration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61050896A JPS62207226A (en) | 1986-03-07 | 1986-03-07 | Pharmaceutical for nasotracheal administration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62207226A true JPS62207226A (en) | 1987-09-11 |
Family
ID=12871502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61050896A Pending JPS62207226A (en) | 1986-03-07 | 1986-03-07 | Pharmaceutical for nasotracheal administration |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62207226A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0565722A1 (en) * | 1990-12-25 | 1993-10-20 | Kyowa Hakko Kogyo Co., Ltd. | Pharmaceutical preparation for pernasal administration |
| US5399341A (en) * | 1990-06-21 | 1995-03-21 | Huland; Edith | Use of cytokin-containing aerosols and the cytokin-containing aerosols |
| EP0505123B1 (en) * | 1991-03-15 | 1997-01-08 | Amgen Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| US5780012A (en) * | 1990-06-21 | 1998-07-14 | Huland; Edith | Method for reducing lung afflictions by inhalation of cytokine solutions |
| US5948414A (en) * | 1998-03-24 | 1999-09-07 | Nouveau Technologies, Inc. | Herbal based nasal spray |
| WO1999066940A1 (en) * | 1996-06-06 | 1999-12-29 | Nouveau Technologies, Inc. | Use of saponins for the treatment of mucosae |
| US8519098B2 (en) | 1998-09-01 | 2013-08-27 | Hoffmann-La Roche Inc. | Composition of a polypeptide and an amphiphilic compound in an ionic complex and the use thereof |
-
1986
- 1986-03-07 JP JP61050896A patent/JPS62207226A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5399341A (en) * | 1990-06-21 | 1995-03-21 | Huland; Edith | Use of cytokin-containing aerosols and the cytokin-containing aerosols |
| US5780012A (en) * | 1990-06-21 | 1998-07-14 | Huland; Edith | Method for reducing lung afflictions by inhalation of cytokine solutions |
| EP0565722A1 (en) * | 1990-12-25 | 1993-10-20 | Kyowa Hakko Kogyo Co., Ltd. | Pharmaceutical preparation for pernasal administration |
| EP0505123B1 (en) * | 1991-03-15 | 1997-01-08 | Amgen Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| WO1999066940A1 (en) * | 1996-06-06 | 1999-12-29 | Nouveau Technologies, Inc. | Use of saponins for the treatment of mucosae |
| US5948414A (en) * | 1998-03-24 | 1999-09-07 | Nouveau Technologies, Inc. | Herbal based nasal spray |
| US8519098B2 (en) | 1998-09-01 | 2013-08-27 | Hoffmann-La Roche Inc. | Composition of a polypeptide and an amphiphilic compound in an ionic complex and the use thereof |
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