JPH0477434A - Preparation of granulocyte colony stimulation factor to be applied to ocular mucous membrane - Google Patents
Preparation of granulocyte colony stimulation factor to be applied to ocular mucous membraneInfo
- Publication number
- JPH0477434A JPH0477434A JP2188736A JP18873690A JPH0477434A JP H0477434 A JPH0477434 A JP H0477434A JP 2188736 A JP2188736 A JP 2188736A JP 18873690 A JP18873690 A JP 18873690A JP H0477434 A JPH0477434 A JP H0477434A
- Authority
- JP
- Japan
- Prior art keywords
- preparation
- granulocyte colony
- csf
- ocular
- mucous membrane
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 210000004400 mucous membrane Anatomy 0.000 title abstract description 3
- 210000003714 granulocyte Anatomy 0.000 title abstract 2
- 230000000638 stimulation Effects 0.000 title abstract 2
- 239000012736 aqueous medium Substances 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 229920001059 synthetic polymer Polymers 0.000 claims abstract description 5
- 210000004877 mucosa Anatomy 0.000 claims description 10
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 6
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- 208000022873 Ocular disease Diseases 0.000 abstract description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004327 boric acid Substances 0.000 abstract description 3
- 239000007853 buffer solution Substances 0.000 abstract description 3
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- 229930195725 Mannitol Natural products 0.000 description 2
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
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- 102100028675 DNA polymerase subunit gamma-2, mitochondrial Human genes 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 101000837415 Homo sapiens DNA polymerase subunit gamma-2, mitochondrial Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 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
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- 206010057249 Phagocytosis Diseases 0.000 description 1
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
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- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
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- 238000002474 experimental method Methods 0.000 description 1
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- 150000004665 fatty acids Chemical class 0.000 description 1
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- 238000004108 freeze drying Methods 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
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- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
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- 239000001632 sodium acetate Substances 0.000 description 1
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- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【発明の詳細な説明】
本主所Ω丘立
本発明は、顆粒球コロニー刺激因子（以後“ＧＣＳ Ｆ
”と略す。）の非注射剤の一種として、眼粘膜に適用
して薬効を得るための製剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the use of granulocyte colony stimulating factor (hereinafter referred to as "GCSF").
It relates to a preparation that is applied to the ocular mucosa to obtain medicinal effects as a type of non-injectable drug.
本生肌夏背景
近年においてはＭ患者、＊器移植患者を始めとして、各
種怒染症の化学療法において耐性菌の発生、菌交代現象
、弱毒菌感染症などが臨床上重大な問題となっており、
そのため抗生物質、合成抗菌剤等による化学療法以外に
、惑染菌宿主の防禦機能を活性化し得る化合物または物
質を用いて上記化学療法の根本的な問題の解決を図ろう
とする療法が注目されている。例えば、細菌感染の初期
には宿主のもつ防禦機能のうち白血球の画賛食作用が最
も強く影響すると考えられており、Ｇ−Ｃ３Ｆを用いて
好中菌の増殖、分化成熟を促進することにより宿主の感
染防禦機能の亢進を図ることが臨床上試みられ、かなり
の成果を上げている。Summer Background In recent years, the development of resistant bacteria, bacterial replacement, and attenuated bacterial infections have become clinically serious problems in chemotherapy for various infectious diseases, including M patients and organ transplant patients. Ori,
Therefore, in addition to chemotherapy using antibiotics, synthetic antibacterial agents, etc., therapies that attempt to solve the fundamental problems of chemotherapy using compounds or substances that can activate the defense function of the host of infectious bacteria are attracting attention. There is. For example, in the early stages of bacterial infection, it is thought that among the host's defensive functions, the phagocytosis of white blood cells is the most influential, and G-C3F can be used to promote the proliferation, differentiation and maturation of neutrophils, thereby preventing the host from becoming infected. Clinical attempts have been made to enhance the infection prevention function of the human body, and considerable results have been achieved.
これまで上記各種感染症患者に対してＣ−Ｃ５Ｆ療法を
実施するに際しては、注射剤を用いて点滴静注、ワンシ
ョット静注もしくは皮下、皮肉注射などが行われている
。しかし注射剤の使用は院内での使用のみに限定され、
自宅療養中の患者への広範囲なＧ−Ｃ３Ｆの適用には注
射剤以外の荊形または製剤が必要となる。既に本出願人
はＧ−Ｃ３Ｆの経口製剤について特願昭６３−１９１１
８５として特許出願中である。しかしながらより広汎な
剤層の提供および眼局所疾患への通用などを考慮すれば
、経口剤以外の製剤への需要が存在する。Until now, C-C5F therapy has been carried out on patients with the various infectious diseases mentioned above, using injections, such as intravenous drip infusion, one-shot intravenous injection, subcutaneous injection, or subcutaneous injection. However, the use of injections is limited to in-hospital use only.
Widespread application of G-C3F to patients receiving home treatment requires other formulations or formulations than injections. The present applicant has already filed a patent application in 1983-1911 regarding the oral preparation of G-C3F.
A patent application is pending as No. 85. However, in view of providing a wider range of drug layers and applicability to local ocular diseases, there is a demand for formulations other than oral formulations.
オ虜Ｕ
本発明は、このような需要を満たすため、眼局所疾患の
処置のため、あるいは適用眼粘膜から吸収後金身性に作
用し得るＧ−Ｃ５Ｆの眼粘膜通用製剤を提供する。SUMMARY OF THE INVENTION In order to meet such demands, the present invention provides an ocular mucosal preparation of G-C5F that can be used to treat local ocular diseases or that can act on the body in a metallic manner after being absorbed from the ocular mucosa to which it is applied.
一面において本発明は、水性媒体中にＧ−Ｃ３Ｆを含有
することを特徴とするＧ−Ｃ３Ｆの眼粘膜適用製剤に関
する。In one aspect, the present invention relates to a formulation of G-C3F for application to the ocular mucosa, characterized by containing G-C3F in an aqueous medium.
他の面において、本発明は、遊離カルボキシル基を有す
る生理的に無害な合成もしくは半合成ポリマーのフィル
ム中にＧ−Ｃ３Ｆを均一に分散してなるＧ−Ｃ３Ｆの眼
粘膜適用製剤に関する。In another aspect, the present invention relates to a formulation of G-C3F for application to the ocular mucosa, which comprises G-C3F uniformly dispersed in a film of a physiologically harmless synthetic or semi-synthetic polymer having free carboxyl groups.
狂１旦梵１隻履探
Ｇ−Ｃ３Ｆは、ヒトＧ−Ｃ３Ｆ産生細胞を培養すること
によっても得られるが、最近遺伝子組換え技術を使用し
て比較的多量に高力価の製品が得られるようになった。G-C3F can also be obtained by culturing human G-C3F-producing cells, but recently genetic recombination technology has been used to obtain a relatively large amount of high-titer product. It became so.
本発明においてはそのいずれも使用することができるが
、例えばＰＣＴ／ＷＯ３７１０１１３２に開示された方
法によって製造した組換えＧ−Ｃ５Ｆを用いるのが好ま
しい。Although any of them can be used in the present invention, it is preferable to use recombinant G-C5F produced by the method disclosed in PCT/WO37101132, for example.
本発明の点眼用液剤は、水性媒体中Ｇ−Ｃ３Ｆを含む。The ophthalmic solution of the present invention contains G-C3F in an aqueous medium.
水性媒体は生理食塩水、または生理的に許容し得る緩衝
液（リン酸、ホウ酸、酢酸など）が−船釣である。点眼
液中のＧ−Ｃ３Ｆの含有量は微量でよく、例えば５μｇ
／ｄ、１０μｇ／ｌｄまたはそれ以上、例えば５０μｇ
／ｌＮ’１Ｍ度でよい。The aqueous medium is physiological saline or a physiologically acceptable buffer (phosphoric acid, boric acid, acetic acid, etc.). The content of G-C3F in the eye drops may be a trace amount, for example, 5 μg.
/d, 10 μg/ld or more, e.g. 50 μg
/lN' 1M degree is sufficient.
点眼液はＧ−Ｃ３Ｆの眼粘膜吸収を助けるため非イオン
界面活性剤を含むことができ、それらは使用濃度におい
て生理的に無害である限り公知のものを使用し得る。そ
のような界面活性剤の例は、ソルビタン脂肪酸エステル
、ポリオキシエチレンソルビタン脂肪酸エステル、ポリ
オキシエチレン水素化ヒマシ油、ポリオキシエチレンラ
ノリン、ポリオキシエチレン脂肪アルコールエーテル、
脂肪酸アルカノールアミド、ショ糖脂肪酸エステルなど
がある。その濃度は使用する特定の界面活性剤の種類お
よび点眼液中のＧ−Ｃ３Ｆ濃度に依存するが、一般に少
なくともＧ−Ｃ３Ｆと等しい濃度で使用され、場合によ
り０．１％以上の濃度も使用し得る。点眼液は、所望に
より等張化剤（例えば塩化ナトリウムなど）、緩衝側（
例えばホウ酸、リン酸−水素ナトリウム、リン酸二水素
ナトリウム、酢酸ナトリウムなど）、保存剤（例えば塩
化ベンザルコニウム、塩化ベンゼトニウム、クロロブタ
ノールなど）、安定剤または増粘剤（例えば乳糖、マン
ニトール、マルトース、ヒアルロン酸ナトリウム、コン
ドロイチン硫酸、ポリアクリル酸ナトリウムなど）のよ
うな点眼剤に通常用いられる添加剤を含むことができる
。The eye drops may contain nonionic surfactants to aid absorption of G-C3F into the ocular mucosa, and any known nonionic surfactants may be used as long as they are physiologically harmless at the concentration used. Examples of such surfactants are sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene lanolin, polyoxyethylene fatty alcohol ethers,
These include fatty acid alkanolamide and sucrose fatty acid ester. Its concentration depends on the specific surfactant used and the G-C3F concentration in the eye drops, but it is generally used at a concentration at least equal to G-C3F, and in some cases concentrations of 0.1% or higher are used. obtain. The eye drops may optionally contain an isotonic agent (e.g. sodium chloride, etc.), a buffer side (
(e.g. boric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium acetate, etc.), preservatives (e.g. benzalkonium chloride, benzethonium chloride, chlorobutanol, etc.), stabilizers or thickeners (e.g. lactose, mannitol, It may contain additives commonly used in eye drops such as maltose, sodium hyaluronate, chondroitin sulfate, sodium polyacrylate, etc.).
本発明はまた、マトリックスとして遊離カルボキシル基
を有する生理的に無害な合成もしくは半合成ポリマーの
フィルム中にＧ−Ｃ３Ｆを均一に分散してなるＧ−Ｃ３
Ｆの眼粘膜適用固形製剤を提供する。遊離カルボキシル
基を有する合成もしくは半合成ポリマーとは、錠剤、カ
プセル、顆粒等に腸溶性フィルムをコーティングするた
めに用いられるポリマーを意味する。そのようなポリマ
ーの例には、セルロースアセテートフタレート、ヒドロ
キシプロピルメチルセルローススクシネート、ヒドロキ
シプロピルメチルセルロースフタレート、カルボキシメ
チルエチルセルロース、メタクリル酸−メタクリル酸メ
チルコポリマー等がある。本発明の眼粘膜通用製剤は、
これらのポリマーを有機溶媒に溶解し、Ｇ−Ｃ３Ｆの所
望量を加えて分散した後注型し、フィルム状に成形する
ことによって得られる。Ｃ−Ｃ３Ｆは一回の投与量が例
えば１〜５００μｇとなるように添加される。The present invention also provides G-C3F obtained by uniformly dispersing G-C3F in a physiologically harmless synthetic or semi-synthetic polymer film having free carboxyl groups as a matrix.
The present invention provides a solid preparation for application to the ocular mucosa of F. By synthetic or semi-synthetic polymers having free carboxyl groups is meant polymers used for coating tablets, capsules, granules, etc. with enteric films. Examples of such polymers include cellulose acetate phthalate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, methacrylic acid-methyl methacrylate copolymers, and the like. The ocular mucosal preparation of the present invention includes:
These polymers are dissolved in an organic solvent, a desired amount of G-C3F is added and dispersed, and then cast and formed into a film. C-C3F is added in such a manner that a single dose is, for example, 1 to 500 μg.
このフィルム状製剤を眼粘膜へ通用するとき、フィルム
は涙液により膨潤し、溶出したＧ−Ｃ３Ｆが粘膜から吸
収されて比較的長時間その薬効を発揮する。When this film-form preparation is applied to the ocular mucosa, the film swells with lachrymal fluid, and the eluted G-C3F is absorbed through the mucous membrane, exerting its medicinal efficacy for a relatively long period of time.
実施例１
点眼液１００ｄ中
Ｇ＝Ｃ５Ｆ ５０ｍｇマンニ
トール ５００ａ＋ｇＴｗｅｅｎ
８０ （ポリソルベート８０） ４１１１ｇ
ＨＣＯ−６０（ポリオキシエチレン ５０Ｍ水素
化ヒマシ油）
ｌＯｍＭｆＩ￥酸緩衝液、ｐＨ４，０適量酢酸緩衝液の
一部を取り、これへ他の成分を添加してよくかきまぜ、
残りの酢酸緩衝液を全量が１００〆となるように加えて
攪拌、溶解した後、滅菌濾過して点眼液とする。Example 1 G=C5F in 100d eye drops 50mg mannitol 500a+gTween
80 (Polysorbate 80) 4111g
HCO-60 (polyoxyethylene 50M hydrogenated castor oil) lOmMfI acid buffer, pH 4,0 Take a portion of the acetate buffer, add the other ingredients to it, and stir well.
Add the remaining acetate buffer to a total volume of 100%, stir and dissolve, and then sterilize and filter to obtain an eye drop.
四カバ展
上で得られた点眼液剤の１０μｌを体重３００ｇのラッ
トの片眼ずつ双方の眼に点眼により投与した。適用前お
よび通用後４８時間にわたってラット尾動脈より採血し
、血液中の白血球数の動態を観察した。適用前の白血球
数を１とし、通用後４８時間の変化を指数で表わしたグ
ラフを第１図に示す。図から適用後直ちに白血球数が増
加し、１２時間接ピークに達した後、４８時間以上効力
が持続することがわかる。10 .mu.l of the eye drop obtained on Shikaba was administered to each eye of a rat weighing 300 g, one eye at a time. Blood was collected from the rat tail artery before and 48 hours after application, and the dynamics of the number of white blood cells in the blood was observed. FIG. 1 shows a graph in which the number of white blood cells before application is set to 1 and the changes 48 hours after application are expressed as an index. From the figure, it can be seen that the white blood cell count increases immediately after application, reaches a peak at 12 hours, and then remains effective for 48 hours or more.
実施例２
フィルム ゛ ノ＋１
あらかしめ凍結乾燥を施したＧ−Ｃ３Ｆ５００μｇまた
は２５０μｇと、ＨＰ５５（ヒドロキプ４゜ロピルメチ
ルセルロースフタレート）１００ｕｇとをメタノール：
液化メチレン（３：１０）混液０、７５ ｄ中に溶解す
る。溶液をガラス製の型に流し込み、風乾してフィルム
状製剤を得る。Example 2 Film ゛ No+1 500 μg or 250 μg of G-C3F subjected to rough freeze-drying and 100 μg of HP55 (hydrocypyl methyl cellulose phthalate) were mixed with methanol:
Dissolve in liquefied methylene (3:10) mixture 0.75 d. The solution is poured into a glass mold and air-dried to obtain a film-like preparation.
四力跋脹
作成したフィルム製剤を５等分に切断し、ペンドパルビ
タール麻酔上体重３００ｇのラットの下まぶた粘膜上に
適用する。適用前および適用後７２時間にわたってラッ
ト尾動脈より採血し、血液中の白血球数の動態を観察し
た。対照ラット群としてはＧ−Ｃ３Ｆを含有しないブラ
シボーフィルム裂開を作成し、投与群と同様な実験を行
った。The prepared film preparation was cut into 5 equal parts and applied to the lower eyelid mucosa of a rat weighing 300 g under pendoparbital anesthesia. Blood was collected from the rat tail artery before and 72 hours after application, and the dynamics of the number of white blood cells in the blood was observed. As a control rat group, a Brasibaugh film dehiscence not containing G-C3F was prepared, and the same experiment as the administration group was conducted.
適用前の白血球数を１とし、適用後７２時間の変化を指
数で表わしたグラフを第２〜４図に示す。Figures 2 to 4 show graphs in which the number of white blood cells before application is set to 1 and the changes 72 hours after application are expressed as an index.
第２図は対照群（ブラシボー）、第３図は低用量（５０
μｇ）群、第４図は高用量（１００μｇ）群である。血
中の白血球数はＧ−Ｃ３Ｆのフィルム製剤適用後上昇し
、その上昇の割合には投与量に比例したレスポンスが認
められる。Figure 2 is the control group (Brasibau), Figure 3 is the low dose (50
FIG. 4 is the high dose (100 μg) group. The number of white blood cells in the blood increases after application of the G-C3F film preparation, and the rate of increase shows a response proportional to the dose.
第１図はラットへ点眼液としてＧ−Ｃ３Ｆを投与したと
きの血中白血球数の動態を示すグラフ、第２図、第３図
および第４図は眼粘膜適用フィルム製剤としてＧ−Ｃ３
Ｆを投与したときの血中白血球数の動態を示すグラフで
あり、第２図は対照群、第３図は低用量群、第４図は高
用量群である。
１１１図
第２図
第３図
第４図Figure 1 is a graph showing the dynamics of the number of blood leukocytes when G-C3F is administered as an eye drop to rats.
FIG. 2 is a graph showing the dynamics of the number of blood leukocytes when administering F. FIG. 2 is a control group, FIG. 3 is a low-dose group, and FIG. 4 is a high-dose group. 111Figure 2Figure 3Figure 4
Claims (2)
ることを特徴とする顆粒球コロニー刺激因子の眼粘膜適
用液剤。(1) A solution for application to the ocular mucosa of granulocyte colony-stimulating factor, which contains granulocyte colony-stimulating factor in an aqueous medium.
もしくは半合成ポリマーのフィルム中に顆粒球コロニー
刺激因子を均一に分散してなる顆粒球コロニー刺激因子
の眼粘膜適用固形製剤。(2) A solid preparation of granulocyte colony-stimulating factor for application to the ocular mucosa, which is obtained by uniformly dispersing granulocyte colony-stimulating factor in a physiologically harmless synthetic or semi-synthetic polymer film having free carboxyl groups.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2188736A JPH0477434A (en) | 1990-07-17 | 1990-07-17 | Preparation of granulocyte colony stimulation factor to be applied to ocular mucous membrane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2188736A JPH0477434A (en) | 1990-07-17 | 1990-07-17 | Preparation of granulocyte colony stimulation factor to be applied to ocular mucous membrane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0477434A true JPH0477434A (en) | 1992-03-11 |
Family
ID=16228875
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2188736A Pending JPH0477434A (en) | 1990-07-17 | 1990-07-17 | Preparation of granulocyte colony stimulation factor to be applied to ocular mucous membrane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0477434A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994014466A1 (en) * | 1992-12-18 | 1994-07-07 | Boehringer Mannheim Gmbh | Aqueous pharmaceutical preparations of g-csf with a long shelf life |
| WO1994021276A1 (en) * | 1993-03-17 | 1994-09-29 | Otsuka Pharmaceutical Co., Ltd. | Agent for preventing and treating digestive mucosal disorders |
| WO1995003784A1 (en) * | 1993-07-28 | 1995-02-09 | Insite Vision Incorporated | Suspensions for delivery of medicament |
| WO1997012598A3 (en) * | 1995-10-06 | 1997-05-15 | Mendes Srl | Dermatological and cosmetic compositions suitable for topical application, having modulating effect on the endogenous ceramide of the skin |
| JP2015509495A (en) * | 2012-02-24 | 2015-03-30 | ボシュ・アンド・ロム・インコーポレイテッドＢａｕｓｃｈ ＆ Ｌｏｍｂ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ophthalmic composition having an alkoxylated natural wax |
-
1990
- 1990-07-17 JP JP2188736A patent/JPH0477434A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994014466A1 (en) * | 1992-12-18 | 1994-07-07 | Boehringer Mannheim Gmbh | Aqueous pharmaceutical preparations of g-csf with a long shelf life |
| AU692430B2 (en) * | 1992-12-18 | 1998-06-11 | Amgen, Inc. | Aqueous pharmaceutical preparations of G-CSF with a long shelf life |
| KR100266146B1 (en) * | 1992-12-18 | 2000-09-15 | 헤르베르트 포우퀘트 | Aqueous pharmaceutical preparations of g-csf with a long shelf life |
| AU692430C (en) * | 1992-12-18 | 2007-09-20 | Amgen, Inc. | Aqueous pharmaceutical preparations of G-CSF with a long shelf life |
| WO1994021276A1 (en) * | 1993-03-17 | 1994-09-29 | Otsuka Pharmaceutical Co., Ltd. | Agent for preventing and treating digestive mucosal disorders |
| WO1995003784A1 (en) * | 1993-07-28 | 1995-02-09 | Insite Vision Incorporated | Suspensions for delivery of medicament |
| WO1997012598A3 (en) * | 1995-10-06 | 1997-05-15 | Mendes Srl | Dermatological and cosmetic compositions suitable for topical application, having modulating effect on the endogenous ceramide of the skin |
| JP2015509495A (en) * | 2012-02-24 | 2015-03-30 | ボシュ・アンド・ロム・インコーポレイテッドＢａｕｓｃｈ ＆ Ｌｏｍｂ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ophthalmic composition having an alkoxylated natural wax |
| US9375401B2 (en) | 2012-02-24 | 2016-06-28 | Bausch ÷ Lomb Incorporated | Ophthalmic compositions with alkoxylated natural waxes |
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