JPH0121132B2 - - Google Patents
Info
- Publication number
- JPH0121132B2 JPH0121132B2 JP54173974A JP17397479A JPH0121132B2 JP H0121132 B2 JPH0121132 B2 JP H0121132B2 JP 54173974 A JP54173974 A JP 54173974A JP 17397479 A JP17397479 A JP 17397479A JP H0121132 B2 JPH0121132 B2 JP H0121132B2
- Authority
- JP
- Japan
- Prior art keywords
- glycerylphosphorylcholine
- rats
- antilipidemic
- administered
- test
- 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.)
- Expired
Links
- 239000008777 Glycerylphosphorylcholine Substances 0.000 claims description 17
- 239000003524 antilipemic agent Substances 0.000 claims description 8
- 229960004956 glycerylphosphorylcholine Drugs 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000006186 oral dosage form Substances 0.000 claims 1
- 239000006201 parenteral dosage form Substances 0.000 claims 1
- 241000700159 Rattus Species 0.000 description 14
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 235000021588 free fatty acids Nutrition 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 150000005830 nonesterified fatty acids Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 230000004130 lipolysis Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- VAPZPBBPRKQWNR-AKGZTFGVSA-N OCC(O)CP(=O)=N[C@@H](CO)C(O)=O Chemical compound OCC(O)CP(=O)=N[C@@H](CO)C(O)=O VAPZPBBPRKQWNR-AKGZTFGVSA-N 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000002114 anti-triglyceridemic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- FRMZOWIQVCBEAC-UHFFFAOYSA-N glycerylphosphorylethanolamine Chemical compound OCCN(P(O)(O)=O)CC(O)CO FRMZOWIQVCBEAC-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Description
本発明は、抗脂肪血症剤に関する。さらに詳し
くは、式（）：
を有するグリセリルホスホリルコリンを有効成分
とする抗脂肪血症剤に関する。
グリセリルホスホリルコリンは正常な代謝産物
として人体内に存在しており、体内における中間
代謝により、グリセリルホスホリルエタノールア
ミンまたはグリセリルホスホリルセリンに相互転
化することが知られている。
本発明に用いるグリセリルホスホリルコリンは
レシチン、とくに卵からえられたレシチンを加水
分解することによつてうることができる。
つぎに試験例および処方例をあげて本発明を詳
細に説明する。
試験例 １
（急性毒性試験）
(1) 経口投与
Ｌ−α−グリセリルホスホリルコリンをハツ
カネズミ、ネズミおよびウサギに経口投与した
結果、いずれも死なず、また投与量３ｇ／Kgま
では何の症状も現われなかつた。
(2) 腹腔内投与
Ｌ−α−グリセリルホスホリルコリンをネズ
ミ、ハツカネズミおよびウサギに腹腔内投与し
た結果、ネズミおよびハツカネズミにおける
LD50は最大で1500mg／Kgであり、ウサギにお
けるLD50は1000mg／Kgであつた。
(3) 筋肉内投与
Ｌ−α−グリセリルホスホリルコリンをネズ
ミ、ハツカネズミおよびウサギに筋肉内投与し
た結果、ネズミにおけるLD50は約1300mg／Kg、
ハツカネズミにおけるLD50は約1000mg／Kg、
ウサギにおけるLD50は約600mg／Kgであつた。
試験例 ２
（抗脂肪血症作用）
(1) ブチヤナンのテスト（Buchanan′s test）
平均体重200ｇの雄ネズミ20匹に、Ｌ−α−
グリセリルホスホリルコリンを４日間連続して
毎日100mg／Kgまたは200mg／Kgずつ筋肉内投与
した。
その結果、血液のコレステロールが投与量
100mg／Kg／日のばあい10％、投与量200mg／
Kg／日のばあいは17％減少し、一方、α−リポ
タンパク質はそれぞれ17％および40％増加し
た。これらの結果は、無処理の10匹のネズミと
比較したものである。
叙上の結果と同時に、予想どおりα−リポタ
ンパク質とは異なつて動脈硬化症を惹起する
（atherogenic）ものとして知られているβ−リ
ポタンパク質の割合がかなり減少した。
(2) エタノール摂取
Ｌ−α−グリセリルホスホリルコリン100
mg／Kg／日を４日間連続して、平均体重200ｇ
の雄ネズミ20匹および平均体重170ｇの雌ネズ
ミ20匹に腹腔内投与した。
投与を開始した翌日に10％のエタノール水溶
液を任意量投与し、第３日目および第４日目に
はそれぞれ胃探針（gastric probe）により各
ネズミにエタノール0.5ｇをさらに投与した。
血液のトリグリセライドは、エタノールだけの
処置を施した比較用のネズミ（雄雌各10匹）に
比較して正味雄ネズミでは38％、雌ネズミでは
45％減少した。
(3) 断食の際の脂肪分解
平均体重195ｇの雄ネズミを20匹ずつ３グル
ープに分け、Ｌ−α−グリセリルホスホリルコ
リンをそれぞれ100mg／Kg、200mg／Kgおよび
400mg／Kg腹腔内投与して48時間の断食を開始
した。断食の間は水のみ任意量与えた。断食開
始24時間後、各グループへ最初と同量のＬ−α
−グリセリルホスホリルコリンを投与した。
断食終了後、ネズミを解剖したところ
NEFA（エステル化されていない脂肪酸（Not
Esterified Fatty Acids））の減少がみられた。
その割合は、各グループに10匹ずついた比較用
のネズミに比して、投与量100mg／Kgのグルー
プでは７％、投与量200mg／Kgのグループでは
11％および投与量400mg／Kgのグループでは21
％であつた。
試験例 ３
（薬物動力学的（Pharmacokinetic）考察）
ブチヤナンのテストにおけるα−リポタンパク
質の増加作用およびβ−リポタンパク質の減少作
用、エタノール摂取における血液のトリグリセラ
イドの減少作用および断食の際の脂肪分解におけ
るNEFAの減少作用を解明するために識別でき
るＬ−α−グリセリルホスホリルコリンを用いて
実験を行なつた。
識別用Ｌ−α−グリセリルホスホリルコリンを
静脈内、筋肉内および経口投与すると、いずれの
ばあいにも循環系内にほぼすべての識別用物質が
見出され、識別用Ｌ−α−グリセリルホスホリル
コリンが完全にかつ迅速に再吸収されることが判
明した。
さらに少なくとも50％の識別用物質が最初の１
時間のうちに循環系から消え、それに相当する量
が肝臓内に見出された（一部脳内にも存在してい
た）。投与してから３〜４時間後、識別用物質が
循環系に戻つてきはじめ、６時間後には80〜90％
がリポタンパク質内に含まれて戻つてきた。それ
はＬ−α−グリセリルホスホリルコリンがリポタ
ンパク質の合成に用いられていることを示してい
る。また100時間経過後も循環系内に６時間後の
ばあいとほぼ同量の放射能が検出された。
それらの結果からＬ−α−グリセリルホスホリ
ルコリンは抗脂肪血症剤として働くことが考察さ
れ、他の抗脂肪血症剤ほど激しくはないが、急
性、亜急性および慢性毒性がないという性質と相
いまつてきわめてよい効果を発揮することが見出
された。
試験例 ４
（臨床試験）
試験例１〜３で示された薬理作用について臨床
試験を行なつた結果の報告をつぎに示す（血清を
清澄化する抗リポタンパク質症
（antidislipoproteinic）作用および抗トリグリセ
ライド症（antitriglyceridemic）作用）。
脂肪血症によつて惹起された種々の症状を示す
20名の患者にＬ−α−グリセリルホスホリルコリ
ンを投与した結果、トリグリセライド症
（triglyceridaemia）の症状を抑制し、α−リポ
タンパク質とβ−リポタンパク質との関係を改善
するという顕著な効果を示した。
叙上の毒性試験、薬理試験および臨床試験の結
果は、本発明に用いる式（）を有する化合物が
脂肪血症の治療にきわめて有用なものであること
を示している。
本発明の抗脂肪血症剤は式（）を有する化合
物を有効成分とするものであり、それの剤形の際
に薬理的に許容しうる担体と公知の方法で組合せ
て調合物としてもよい。必要ならば投与単位ごと
に剤形してもよく、そのばあい１単位に含有され
る有効成分の量は１またはそれ以上の単位を投与
することによつて治療効果が発揮できるようにす
るのが好ましい。剤形としては、たとえばタブレ
ツト、丸剤、香粉、小包、カプセルなどの経口用
剤、坐薬および必要ならばアンプル入りの無菌注
射用液または懸濁液などの非経口剤などがあげら
れる。
なお本発明による抗脂肪血症剤のヒトに対する
有効投与量は、経口では0.6〜1.2ｇ／日を２〜３
回に分けて投与、静注または筋注では0.4〜1.2
ｇ／日を１〜２回に分けて投与であつた。
つぎに本発明の治療剤の処方例をあげる。
TECHNICAL FIELD The present invention relates to antilipidemic agents. For more details, the formula (): The present invention relates to an antilipidemic agent containing glycerylphosphorylcholine as an active ingredient. Glycerylphosphorylcholine exists in the human body as a normal metabolite, and is known to be interconverted into glycerylphosphorylethanolamine or glycerylphosphorylserine through intermediate metabolism in the body. Glycerylphosphorylcholine used in the present invention can be obtained by hydrolyzing lecithin, particularly lecithin obtained from eggs. Next, the present invention will be explained in detail by giving test examples and prescription examples. Test Example 1 (Acute Toxicity Test) (1) Oral Administration When L-α-glycerylphosphorylcholine was orally administered to mice, mice, and rabbits, none of them died, and no symptoms appeared up to a dose of 3 g/Kg. Ta. (2) Intraperitoneal administration As a result of intraperitoneal administration of L-α-glycerylphosphorylcholine to rats, mice, and rabbits,
The LD 50 was up to 1500 mg/Kg, and the LD 50 in rabbits was 1000 mg/Kg. (3) Intramuscular administration As a result of intramuscular administration of L-α-glycerylphosphorylcholine to rats, mice, and rabbits, the LD 50 in rats was approximately 1300 mg/Kg,
LD 50 in Mus musculus is approximately 1000 mg/Kg;
The LD 50 in rabbits was approximately 600 mg/Kg. Test Example 2 (Antilipidemia effect) (1) Buchanan's test 20 male rats with an average weight of 200 g were given L-α-
Glycerylphosphorylcholine was administered intramuscularly at 100 mg/Kg or 200 mg/Kg daily for 4 consecutive days. As a result, the cholesterol in the blood becomes
10% if 100mg/Kg/day, dosage 200mg/
Kg/day decreased by 17%, while α-lipoprotein increased by 17% and 40%, respectively. These results were compared to 10 untreated rats. Simultaneously with the above results, as expected, the proportion of β-lipoprotein, which is known to be atherogenic in contrast to α-lipoprotein, was significantly reduced. (2) Ethanol intake L-α-glycerylphosphorylcholine 100
mg/Kg/day for 4 consecutive days, average body weight 200g
The drug was administered intraperitoneally to 20 male rats and 20 female rats with an average weight of 170 g. An arbitrary amount of 10% ethanol aqueous solution was administered on the day after the start of administration, and on the third and fourth days, 0.5 g of ethanol was further administered to each mouse using a gastric probe.
Blood triglycerides were 38% lower in male rats and 38% lower in female rats compared to control rats (10 male and female) treated with ethanol only.
decreased by 45%. (3) Lipolysis during fasting Male rats with an average weight of 195 g were divided into 3 groups of 20 and treated with L-α-glycerylphosphorylcholine at 100 mg/Kg, 200 mg/Kg and 200 mg/Kg, respectively.
A 48-hour fast was started after intraperitoneal administration of 400 mg/Kg. During the fast, only water was given ad libitum. 24 hours after the start of the fast, each group received the same amount of L-α as at the beginning.
-Glycerylphosphorylcholine was administered. After fasting, the rat was dissected.
NEFA (Non-esterified fatty acids)
A decrease in Esterified Fatty Acids) was observed.
The rate was 7% in the 100 mg/Kg group and 7% in the 200 mg/Kg group compared to the comparison rats with 10 rats in each group.
11% and 21 in the 400 mg/Kg dose group
It was %. Test Example 3 (Pharmacokinetic considerations) In the butyanan test, the effect of increasing α-lipoprotein and decreasing effect of β-lipoprotein, the effect of reducing blood triglyceride in ethanol intake, and the effect on lipolysis during fasting. In order to elucidate the reducing effect of NEFA, experiments were conducted using L-α-glycerylphosphorylcholine, which can be identified. When L-α-glycerylphosphorylcholine for identification is administered intravenously, intramuscularly and orally, almost all of the identification substance is found in the circulatory system in each case, and L-α-glycerylphosphorylcholine for identification is completely removed. It was found that it was reabsorbed quickly and quickly. Furthermore, at least 50% of the identification material is present in the first
It disappeared from the circulation in time, and a comparable amount was found in the liver (and some in the brain). Three to four hours after administration, the identification substance begins to return to the circulation, and by six hours, 80 to 90% of the identification substance has returned to the circulation.
is returned contained within lipoproteins. It shows that L-α-glycerylphosphorylcholine is used in the synthesis of lipoproteins. Furthermore, approximately the same amount of radioactivity was detected in the circulatory system even after 100 hours had passed as that after 6 hours. These results suggest that L-α-glycerylphosphorylcholine acts as an antilipidemic agent, which is not as severe as other antilipidemic agents, but is consistent with its lack of acute, subacute, and chronic toxicity. It has been found that this method has extremely good effects. Test Example 4 (Clinical Test) The following is a report of the results of a clinical test regarding the pharmacological effects shown in Test Examples 1 to 3 (antidislipoproteinic action to clarify serum and antitriglyceridosis). (antitriglyceridemic) action). Showing various symptoms caused by lipemia
The administration of L-α-glycerylphosphorylcholine to 20 patients showed remarkable effects in suppressing the symptoms of triglyceridaemia and improving the relationship between α-lipoprotein and β-lipoprotein. The results of the toxicity, pharmacology and clinical studies described above indicate that the compounds having formula () used in the present invention are extremely useful in the treatment of lipemia. The antilipidemia agent of the present invention has a compound having the formula () as an active ingredient, and may be combined with a pharmacologically acceptable carrier by a known method to form a preparation. . If necessary, they may be formulated in dosage units, in which case the amount of active ingredient contained in each unit is such that the therapeutic effect can be exerted by administering one or more units. is preferred. Dosage forms include, for example, oral preparations such as tablets, pills, sachets, sachets, capsules, parenteral preparations such as suppositories and, if necessary, sterile injectable solutions or suspensions in ampoules. The effective dose for humans of the antilipidemic agent according to the present invention is 0.6 to 1.2 g/day for 2 to 3 days.
Administered in divided doses, 0.4 to 1.2 for IV or IM injections
The dosage was divided into 1 to 2 doses per day. Next, prescription examples of the therapeutic agent of the present invention will be given.
【表】【table】
【表】【table】
【表】【table】
【表】
ンゾエート
[Table] Nzoate
Claims (1)
とする抗脂肪血症剤。 ２ 薬理的に許容しうる担体を加えてなる特許請
求の範囲第１項記載の抗脂肪血症剤。 ３ 経口用に剤形してなる特許請求の範囲第２項
記載の抗脂肪血症剤。 ４ 非経口用に剤形してなる特許請求の範囲第２
項記載の抗脂肪血症剤。[Claims] 1 Formula (): An antilipidemic agent containing glycerylphosphorylcholine as an active ingredient. 2. The antilipidemic agent according to claim 1, which contains a pharmacologically acceptable carrier. 3. The antilipidemia agent according to claim 2, which is in an oral dosage form. 4. Claim 2, which is in a parenteral dosage form
Antilipidemic agents as described in Section 1.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT25706/79A IT1123142B (en) | 1979-09-14 | 1979-09-14 | USE OF GLYCERYLPHOSPHORIL DERIVATIVES IN THE THERAPY OF DYSLIPEMIA AND HEPATITIS, AND RELATED PHARMACEUTICAL COMPOSITIONS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5643212A JPS5643212A (en) | 1981-04-21 |
| JPH0121132B2 true JPH0121132B2 (en) | 1989-04-19 |
Family
ID=11217502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17397479A Granted JPS5643212A (en) | 1979-09-14 | 1979-12-27 | Treating agent for lipemia* alcoholism* acute* subacute and chronic hepatitis* obesity and similar pathological symtoms |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5643212A (en) |
| AU (1) | AU520245B2 (en) |
| BE (1) | BE881071A (en) |
| CH (1) | CH645543A5 (en) |
| DE (1) | DE3000139C2 (en) |
| FR (1) | FR2464715A1 (en) |
| GB (1) | GB2057872B (en) |
| IT (1) | IT1123142B (en) |
| NL (1) | NL179873C (en) |
| ZA (1) | ZA796882B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1199972B (en) * | 1985-05-08 | 1989-01-05 | Lpb Ist Farm | PHARMACEUTICAL COMPOSITIONS FOR THE THERAPY OF INVOLUTIVE CEREBRAL SYNDROMES AND MENTAL DECAY |
| EP0229128B1 (en) * | 1985-07-03 | 1990-05-30 | Cl Pharma Aktiengesellschaft | Derivatives of glycero-3(2)-phospho-l-serine and pharmaceutical preparations containing them |
| IT1213034B (en) * | 1986-02-12 | 1989-12-07 | Istituto Chemioterapico Di Lod | PHARMACEUTICAL COMPOSITIONS FOR THE ORGANIC AND FUNCTIONAL BASIS OF CEREBROPATHIES. |
| IT1212137B (en) * | 1987-04-08 | 1989-11-08 | Rosanna Lodi | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CEREBRAL PSYCHO-ORGANIC SYNDROMES. |
| EP0329053A1 (en) * | 1988-02-15 | 1989-08-23 | MAGIS FARMACEUTICI S.p.A. | Choline esters of glycerophosphoric acids |
| EP0348859A1 (en) * | 1988-07-01 | 1990-01-03 | MAGIS FARMACEUTICI S.p.A. | 1,2-di-O-acyl glycero(DI)phosphate of L-carnitine and its derivatives, a process for their preparation and pharmaceutical formulations which contain them |
| IT1230140B (en) * | 1989-05-03 | 1991-10-14 | Fidia Spa | SERINA DERIVATIVES, THEIR PROCESS OF PREPARATION AND USE IN HUMAN THERAPY |
| JP4891522B2 (en) * | 2003-10-03 | 2012-03-07 | 株式会社ファンケル | Serum GOT, GPT improving agent |
| CN102138892B (en) * | 2010-02-03 | 2014-07-30 | 广州汉光医药进出口有限公司 | Choline alfoscerate injection preparation as well as preparation method and detection method thereof |
| JP2014051459A (en) * | 2012-09-07 | 2014-03-20 | Nof Corp | Fat metabolism enhancer |
| CN116966191A (en) * | 2022-04-22 | 2023-10-31 | 深圳先进技术研究院 | Glycerol phosphorylcholine regulates cellular NAD + Application in level and distribution |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54117034A (en) * | 1978-02-28 | 1979-09-11 | Nippon Shoji Kk | Treating agent for consciousness and perception motion disorder |
-
1979
- 1979-09-14 IT IT25706/79A patent/IT1123142B/en active
- 1979-12-12 GB GB7942835A patent/GB2057872B/en not_active Expired
- 1979-12-13 AU AU53792/79A patent/AU520245B2/en not_active Ceased
- 1979-12-19 ZA ZA00796882A patent/ZA796882B/en unknown
- 1979-12-27 JP JP17397479A patent/JPS5643212A/en active Granted
-
1980
- 1980-01-04 DE DE3000139A patent/DE3000139C2/en not_active Expired
- 1980-01-09 NL NLAANVRAGE8000140,A patent/NL179873C/en not_active IP Right Cessation
- 1980-01-10 BE BE2/58326A patent/BE881071A/en not_active IP Right Cessation
- 1980-01-17 FR FR8001004A patent/FR2464715A1/en active Granted
- 1980-02-05 CH CH89980A patent/CH645543A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5643212A (en) | 1981-04-21 |
| IT1123142B (en) | 1986-04-30 |
| AU5379279A (en) | 1981-04-02 |
| IT7925706A0 (en) | 1979-09-14 |
| BE881071A (en) | 1980-05-02 |
| GB2057872A (en) | 1981-04-08 |
| NL8000140A (en) | 1981-03-17 |
| DE3000139A1 (en) | 1981-04-02 |
| FR2464715A1 (en) | 1981-03-20 |
| DE3000139C2 (en) | 1986-05-22 |
| CH645543A5 (en) | 1984-10-15 |
| GB2057872B (en) | 1984-01-11 |
| ZA796882B (en) | 1980-11-26 |
| NL179873B (en) | 1986-07-01 |
| FR2464715B1 (en) | 1983-07-22 |
| AU520245B2 (en) | 1982-01-21 |
| NL179873C (en) | 1986-12-01 |
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