JPS62223121A - Water soluble medicinal composition based on amino acid saltof (-)cis-1,2-epoxypropylphosphonic acid - Google Patents
Water soluble medicinal composition based on amino acid saltof (-)cis-1,2-epoxypropylphosphonic acidInfo
- Publication number
- JPS62223121A JPS62223121A JP60219969A JP21996985A JPS62223121A JP S62223121 A JPS62223121 A JP S62223121A JP 60219969 A JP60219969 A JP 60219969A JP 21996985 A JP21996985 A JP 21996985A JP S62223121 A JPS62223121 A JP S62223121A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- acid
- cis
- epoxypropylphosphonic
- water soluble
- 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
- 150000001413 amino acids Chemical class 0.000 title claims description 15
- 239000000203 mixture Substances 0.000 title claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000004475 Arginine Substances 0.000 claims description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- -1 amino acid salt Chemical class 0.000 claims description 2
- 235000001014 amino acid Nutrition 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001484 arginines Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229960000308 fosfomycin Drugs 0.000 description 2
- YMDXZJFXQJVXBF-STHAYSLISA-N fosfomycin Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O YMDXZJFXQJVXBF-STHAYSLISA-N 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65502—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a three-membered ring
- C07F9/65505—Phosphonic acids containing oxirane groups; esters thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
本発明は、腸管外でか、或は溶液状でも段′ｊできる抗
生物質としての活性を自する医薬組成物に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to pharmaceutical compositions with antibiotic activity that can be administered parenterally or in solution.
イタリー持１；１出願 Ｎｏ．４１００２ Ａ／７８及
び２８３０４ ｋｌ１８式中Ａ式中側えばリジン、アル
ギニン、オルニチン、／ステイン、メチオニン、グリシ
ン、コリン、アラニン、ベタイン等のアミノ酸であり、
一方アニオン部分は（−） ／スー１． ２−エポキ
ンプロビルホスホン酸である、で示される塩であって、
一船名ホスホマイ／ンとしても知られており、その抗生
物質としての性質により、ヒト及び家畜の治療に使用で
きる化合物が説明されている。Italy has 1; 1 application No. 41002 A/78 and 28304 kl18 In the formula A, the middle side is an amino acid such as lysine, arginine, ornithine, /steine, methionine, glycine, choline, alanine, betaine, etc.
On the other hand, the anion part is (-) / Sue 1. 2-epoquineprobylphosphonic acid, a salt represented by
Also known as fosfomycin, its antibiotic properties describe a compound that can be used in the treatment of humans and livestock.
殊に、ホスホマイノンのアルギニン塩は、予期できない
極めてイ『益な治療上の性質を汀していることが知られ
ている。In particular, the arginine salt of phosphomynon is known to possess unexpected and extremely beneficial therapeutic properties.
（Ｉ）式の化合物は、（−）／スー１，２ーエポキシプ
ロピルホスホン酸とアミノ酸との実際上、当量を、殊に
水溶液か、又はメチル−又はエチルアルコールの水性ア
ルコール溶液中で反応させること（イタリー特許出願
Ｎｏ．４１００２ Ａ／７８及び２Ｇ３０４ Ａ／７８
に説明されている）により製造される。Compounds of formula (I) are obtained by reacting practically equivalent amounts of (-)/su-1,2-epoxypropylphosphonic acid and an amino acid, especially in aqueous solution or in an aqueous alcoholic solution of methyl- or ethyl alcohol. (Italian patent application
No. 41002 A/78 and 2G304 A/78
(described in ).
しかし、こうして得られた化合物は、極めて溶解し難い
ことが判明したので、腸管外投与（血管内）及び溶液と
してでは問題がある。反面、抗生物質治療の臨床医療に
おいては、その様な投与方法は極めて行進のものである
。However, the compounds thus obtained have been found to be extremely difficult to dissolve and are therefore problematic for parenteral administration (intravascularly) and as solutions. On the other hand, in clinical medicine for antibiotic treatment, such administration methods are extremely advanced.
今、（Ｉ）式の化合物、殊に式中Ａがアルギニンをα味
する（Ｉ）式の化合物が、適当過剰量の塩形成アミノ酸
を、その塩製造に際して、或は薬剤網形に最終的に調剤
する直前に添加することによって、１０ないし２０重量
／容量％の水溶性を何する水溶性組成物に適切に製剤で
きることが見出された。Now, a compound of formula (I), especially a compound of formula (I) in which A is arginine, may be used to produce a suitable excess amount of a salt-forming amino acid during the preparation of the salt or as a final product in the form of a drug network. It has been found that water-soluble compositions having a water solubility of 10 to 20% w/v can be suitably formulated by adding the compound just prior to formulation.
アミノ酸は約０．４〜０．８、殊に約０．６モル割合の
過剰を加えるのが良い。The amino acid is preferably added in an excess of about 0.4 to 0.8, particularly about 0.6 molar excess.
塩（Ｉ）のカチオンを形成するものと同しアミノ酸、或
はそれと穴なるアミノ酸を添加することができる。本発
明により得られる溶液のｐＨ−値は生理的に認められる
値、即ち約６．９〜７．４の間にある。The same amino acid as that forming the cation of salt (I), or an amino acid different from it, can be added. The pH value of the solution obtained according to the invention lies within physiologically acceptable values, ie between approximately 6.9 and 7.4.
既述の様に、アミノ酸および過剰の（塩に変成すること
のない）同−及び／又は異種のアミノ酸を用いる塩形成
により得られた、本発明の対象たるホスホマイ７ンの製
剤は、類似の塩類より優れた本溶性の高さにより、また
経口的に投与しても極めて高められ、且つ極めて長時間
の活性型の抗生物質の血液値が得られることによって優
れている。その上本発明の組成物は、ホスホマイシンの
別の塩に対比して、ルＵや腎臓など２．３の４官につい
て高められた趨性を展開する。他方Ｉｂ物学的性な点で
のホスホマイ／／の仔利な性質は全く損なわれることが
ないし、その広い抗菌スペクトルも劣化することがない
。As already mentioned, the formulation of fosfomyne 7, which is the subject of the present invention, obtained by salt formation using amino acids and an excess of the same and/or different amino acids (without being converted into salts) It is superior because of its high solubility, which is superior to salts, and because it can be administered orally to greatly increase blood levels of active antibiotics for a very long time. Furthermore, the compositions of the present invention develop an enhanced trend for 2.3 tetrafunctional molecules such as LeU and kidney compared to other salts of fosfomycin. On the other hand, the advantageous properties of phosfomy// in terms of Ib physical properties are not impaired in any way, nor is its broad antibacterial spectrum impaired.
本発明による注射することの可能な医薬組成物は、従来
、この分野の専門家に良く知られている様な、適当な賦
形剤を当然、含むことができる。同様にして、」Ｌ記便
用に際し充足されなければならない耐滅菌操作性（Ｓｔ
ｅｒｌｌｌｔａｅｔ） 、耐バイロゲン除去操作性（Ａ
ｐｙｒｏｇｅｎ＋ｚ＋ｔａｅｔ）、そして等公比性（Ｉ
ｓｏｔｏｎｉｚｉｔａｔ）なとの性質をイ「している。The injectable pharmaceutical compositions according to the invention may of course contain suitable excipients, such as are conventionally well known to those skilled in the art. Similarly, the sterilization resistance (St.
erlltaet), virogen removal resistance (A
pyrogen+z+taet), and homogeneity (I
It has the property of being "sotonizitat".
本発明によると、ンロノプ、飲用溶液、ブラウス粉末等
の液伏経［−１医薬組成物の製造も可能になる。According to the present invention, it is also possible to produce liquid phlegm [-1] pharmaceutical compositions such as tablets, drinking solutions, blouse powders, etc.
本発明の組成物は、経口投与の場合には、０．５〜１ｇ
の活性主成分（Ｐｒｉｎｚｉｐｓ）を含有しているが、
腸管外投与の場合は０． １〜０．５ｇの活性主成分を
含有している。In the case of oral administration, the composition of the present invention may be 0.5 to 1 g.
Contains the active ingredient (Prinzips),
0 for parenteral administration. Contains 1-0.5g of active principle.
一回の投与１１は診断の結果、玉篤度、１ミ者の体重及
び状態、如何によって決まる。The amount of administration 11 to be administered depends on the diagnosis, severity, body weight and condition of the patient.
実施猶
（−）７スー１，２−エポキンプロピルホスホン酸とリ
ジン、アルギニンおよびオルニチンとを、それぞれ、イ
タリー特許出願 Ｎｏ、４１００２人／７８及び２６３
０４ 人／７８に記載の方法により、但し、下記表に記
載の過剰割合で反応させ、常法により後処理して本発明
の組成物を得た。No. 7-1,2-epoquinepropylphosphonic acid and lysine, arginine and ornithine, respectively, Italian Patent Application No. 41002/78 and 263
The composition of the present invention was obtained by reacting according to the method described in No. 04/78, but at the excess ratio shown in the table below, and post-processing by a conventional method.
次表には、この方法による名種水溶性アミノ酸の快Ｊｌ
ｌｆ１を及び得られた塩の水溶性及び得られたｐ Ｈ−
（ｄｆを示す。The following table shows the quality of famous water-soluble amino acids produced by this method.
lf1 and the water solubility of the obtained salt and the obtained pH
(Denotes df.
ホスホマイ７ンアルギニン塩（１＋１）及び過剰のアミ
ノ酸とホスホマイノンとの塩を含む医薬組成物アミノ酸
モル比 ｔ８解性 ｐＨ８％
アルギニ７ ０．６ １０ Ｅ３．９３ア
ルギニ７ ０．７２ １３ ７．１リジン
０．５５ ９ ７．００オルニチン ０
．６５ １１ ７．３４１１うまでもな（本発明
は、それら例に限定されるものではない。Pharmaceutical composition containing phosphomynon arginine salt (1+1) and excess salt of amino acid and phosphomynon Amino acid Molar ratio T8 lysis pH 8% Argini 7 0.6 10 E3.93 Argini 7 0.72 13 7.1 Lysine
0.55 9 7.00 Ornithine 0
．． 65 11 7.3411 Of course (the present invention is not limited to these examples).
Claims (4)
）シス−１，２−エポキシプロピルホスホン酸のアミノ
酸塩を含有する水溶性医薬組成物(1) Characterized by containing an excess of amino acids (-
) Water-soluble pharmaceutical composition containing an amino acid salt of cis-1,2-epoxypropylphosphonic acid
酸とアルギニンとの塩を含有する特許請求の範囲１の組
成物(2) The composition of claim 1 containing a salt of (-)cis-1,2-epoxypropylphosphonic acid and arginine.
囲１又は２の組成物(3) The composition according to claim 1 or 2, wherein the excess amino acid is arginine.
ルのモル割合で過剰に存在していることを特徴とする上
記特許請求の範囲の１〜３の何れか一つの組成物(4) The composition according to any one of claims 1 to 3, characterized in that the amino acid is present in excess in a molar proportion of 0.4 to 0.8, in particular about 0.6 mol. thing
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH4792/84A CH660306A5 (en) | 1984-10-05 | 1984-10-05 | WATER-SOLUBLE PHARMACEUTICAL COMPOSITIONS BASED ON SALTS OF (-)CIS-1,2-EPOXYPROPYLPHOSPHONIC ACID WITH AMINO ACIDS. |
| CH4792/84-2 | 1984-10-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62223121A true JPS62223121A (en) | 1987-10-01 |
Family
ID=4282621
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60219969A Pending JPS62223121A (en) | 1984-10-05 | 1985-10-02 | Water soluble medicinal composition based on amino acid saltof (-)cis-1,2-epoxypropylphosphonic acid |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS62223121A (en) |
| KR (1) | KR860003012A (en) |
| AT (1) | AT383736B (en) |
| BE (1) | BE903369A (en) |
| CH (1) | CH660306A5 (en) |
| DE (1) | DE3535356A1 (en) |
| ES (1) | ES8609351A1 (en) |
| FR (1) | FR2571255B1 (en) |
| GB (1) | GB2165152B (en) |
| IT (1) | IT1201479B (en) |
| NL (1) | NL8502712A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54109922A (en) * | 1978-02-02 | 1979-08-29 | Italchemi Spa | *****cis**1*22epoxypropyl phosphonic acid salts* their manufacture and antibiotic chemicaltherapeutical drug containing it as active component |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH310498A (en) * | 1951-11-14 | 1955-10-31 | Waldhof Zellstoff Fab | Process for stabilizing alkali salts of adenosine polyphosphoric acids. |
| DE1767212B1 (en) * | 1967-04-13 | 1971-05-06 | Sumitomo Chemical Co | Process for making injectable drugs |
| US3639590A (en) * | 1967-07-25 | 1972-02-01 | Merck & Co Inc | Antibacterial composition containing (-) (cis-1 2-epoxypropyl) phosphoric acid |
| BE756953A (en) * | 1969-10-02 | 1971-04-01 | Merck & Co Inc | POTENTIALIZATION OF ANTIBIOTICS |
| DE2813814A1 (en) * | 1978-03-31 | 1979-10-18 | Boehringer Mannheim Gmbh | Increasing the enteral reabsorption of pharmaceuticals - by administration together with an aminoacid or a peptide |
| IT1112282B (en) * | 1978-07-19 | 1986-01-13 | Zambon Spa | Bis- (2-AMMONIUM-2-hydroxymethyl-1,3-propanediol) (2R-CIS) - (3-METILOSSIRANIL) phosphonate |
| IT1097578B (en) * | 1978-07-31 | 1985-08-31 | Italchemi Spa | METHOD FOR PREPARING ACID SALTS (-) |
| US4235900A (en) * | 1978-11-15 | 1980-11-25 | E. R. Squibb & Sons, Inc. | Cephradine compositions |
-
1984
- 1984-10-05 CH CH4792/84A patent/CH660306A5/en not_active IP Right Cessation
-
1985
- 1985-10-02 JP JP60219969A patent/JPS62223121A/en active Pending
- 1985-10-03 AT AT0287185A patent/AT383736B/en not_active IP Right Cessation
- 1985-10-03 DE DE19853535356 patent/DE3535356A1/en not_active Withdrawn
- 1985-10-04 GB GB08524550A patent/GB2165152B/en not_active Expired
- 1985-10-04 NL NL8502712A patent/NL8502712A/en not_active Application Discontinuation
- 1985-10-04 ES ES547625A patent/ES8609351A1/en not_active Expired
- 1985-10-04 BE BE2/60807A patent/BE903369A/en not_active IP Right Cessation
- 1985-10-04 IT IT22367/85A patent/IT1201479B/en active
- 1985-10-05 KR KR1019850007328A patent/KR860003012A/en not_active IP Right Cessation
- 1985-10-07 FR FR8514800A patent/FR2571255B1/en not_active Expired
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54109922A (en) * | 1978-02-02 | 1979-08-29 | Italchemi Spa | *****cis**1*22epoxypropyl phosphonic acid salts* their manufacture and antibiotic chemicaltherapeutical drug containing it as active component |
Also Published As
| Publication number | Publication date |
|---|---|
| ATA287185A (en) | 1987-01-15 |
| BE903369A (en) | 1986-02-03 |
| FR2571255B1 (en) | 1988-09-16 |
| KR860003012A (en) | 1986-05-19 |
| GB8524550D0 (en) | 1985-11-06 |
| IT1201479B (en) | 1989-02-02 |
| DE3535356A1 (en) | 1986-04-24 |
| IT8522367A0 (en) | 1985-10-04 |
| NL8502712A (en) | 1986-05-01 |
| ES8609351A1 (en) | 1986-09-01 |
| GB2165152B (en) | 1988-03-16 |
| FR2571255A1 (en) | 1986-04-11 |
| CH660306A5 (en) | 1987-04-15 |
| GB2165152A (en) | 1986-04-09 |
| ES547625A0 (en) | 1986-09-01 |
| AT383736B (en) | 1987-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5185488B2 (en) | 2- (4-Isobutylphenyl) propionic acid pharmaceutical composition | |
| US4352814A (en) | Treatment of hepatic and renal disorders with mixed salts of essential or semi-essential amino acids and nitrogen-free analogs | |
| RU2007101653A (en) | Derivatives of 1-azabicyclo [3.3.1] NONANOV | |
| IE903717A1 (en) | S(+)-ibuprofen-L-amino acid and S(+)-ibuprofen-D-amino acid as onset hastened enhanced analgesics | |
| JP2007514728A (en) | Pregabalin composition | |
| WO2003055481A1 (en) | Organ fibrosis inhibitors | |
| FI120080B (en) | Pharmaceutical compositions with antibiotic activity | |
| AU599034B2 (en) | Furosemide salts | |
| US4185093A (en) | Preparation and method for treatment of hypocalcemia, hypophosphatemia and downer cow syndrome in animals | |
| JPH111487A (en) | Zinc salt of l-ascorbic acid 2-phosphate and its production | |
| JPS6248678B2 (en) | ||
| JP2005526120A (en) | Diclofenac composition for topical treatment of cavity disorders in the oropharynx | |
| KR102111094B1 (en) | Oral solid formulation composition for purgative comprising sodium sulfate anhydrous, potassium sulfate, magnesium sulfate anhydrous and simethicone | |
| US2673827A (en) | Therapeutic ion exchange resin mixture | |
| JPS62223121A (en) | Water soluble medicinal composition based on amino acid saltof (-)cis-1,2-epoxypropylphosphonic acid | |
| PL190779B1 (en) | Method for manufacture of semi-solid pharmaceutical compound containing, as therapeutic agent, the (+)-(s)-2-(3-benzoylphenyl) propionic acid salt with thrometamine and semi-solid pharmaceutical compound containing thrometamol dexketoprophene | |
| JPS62223122A (en) | Water soluble medicinal composition based on amino acid saltof (-)cis-1,2-epoxypropylphosphonic acid | |
| CN1190581A (en) | Complex rifampin injection | |
| JP5376785B2 (en) | Pharmaceutical composition | |
| JP5376786B2 (en) | Nerve cell activation composition | |
| US3062722A (en) | Therapeutic 2-aminoethanethiol orate | |
| JPH09502190A (en) | Encapsulation complex of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen | |
| JP2002504517A (en) | Oral compositions of low dose cytotoxic proteins | |
| WO2002074303A1 (en) | Amino acid compositions for ameliorating kidney failure | |
| GB1564135A (en) | Readily-assimilatable highly-soluble calcium and/or magnesium organic salts |