JP2526073B2 - Abnormal rupture treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Use] The present invention relates to a therapeutic agent for abnormal water rupture containing fibrinogen as an active ingredient.

[Problems to be solved by the prior art and the invention]

The fibrinogen contained in blood flows out from the capillaries on the wound surface together with other blood components when the tissue is injured, filling the spaces between the tissues, and interacts with thrombin in the blood to become insoluble fibrin, which becomes the wound surface. It has the function of sticking together. This adhesive action facilitates the generation of fibroblasts on the wound surface, which eventually become fibrocytes to fix the tissue and heal the wound surface. Thus, fibrinogen, which is effective for wound healing, is provided as a dried fibrinogen (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, standard for biological products) for medical treatment, and is used for the treatment of hypofibrinemia by intravenous administration. In recent years, in the surgical field, there has been an increasing demand for extremely delicate medical techniques and locality of the pharmacological action of the drug used, such as anastomosis of fine tissues such as nerves and microvessels. A fibrinogen preparation (Japanese Patent Application Laid-Open No. 57-149229) having a strong adhesive force when locally administered to a tissue has also been developed.

On the other hand, water rupture (rupture of the follicle) is a symptom of rupture of the embryo and outflow of amniotic fluid. Normal fluid rupture during delivery is a phenomenon in which the follicle reaches the extreme tension due to the accumulation of labor during the opening period, bursts without enduring internal pressure, and ruptures 20 to 30 ml of preamniotic fluid.
It occurs after full dilatation of the external cervix (diameter 5 cm or more).

Such normal rupture is essential at delivery,
Abnormal rupture, for example, 1) early rupture: rupture before the onset of labor pain, 2) early rupture: rupture before labor of the external cervix, even with labor pain, 3) high rupture: rupture above the uterine ostium, 4) pseudo-amniotic fluid : The liquid between the chorion and the amniotic membrane that should disappear disappears until the time of delivery, and rupture of the chorion causes rupture of the fluid, 5) Premature ejaculation of amniotic fluid: The advanced part does not fit the birth canal wall, and rupture of the posterior amniotic fluid. In cases where the rupture of water is delayed and a capsular baby is delivered in the presence of a full-mouthed but tough egg membrane, the delivery process is poor in both cases, and this has serious effects on pregnant women, fetuses, and newborns.

Therefore, it is desired to develop a drug or a treatment method that can treat abnormal water rupture more effectively and easily.

An object of the present invention is to provide a drug that can treat abnormal water rupture more effectively and easily.

[Problems to be solved by the invention]

The present inventor has conducted various studies to develop a drug capable of treating the above-mentioned object, that is, abnormal rupture more effectively and easily, and, by locally administering fibrinogen as an active ingredient, a surprisingly large amount was obtained. The present invention has been completed by finding that the ruptured parts of the fetal organs are joined despite the presence of amniotic fluid.

[Means for solving problems]

The present invention relates to a therapeutic agent for abnormal water rupture containing fibrinogen as an active ingredient.

The agent for treating abnormal water rupture of the present invention is a main agent made of fibrinogen, which is optionally mixed with the following auxiliary agents.

In the present invention, fibrinogen in the main agent composed of fibrinogen is preferably a dry fibrinogen for medical use manufactured according to the biological formulation standard (pages 201 to 203 of 1979) under the supervision of the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare. In addition to fibrinogen, a main agent composed of fibrinogen may be blended with a stabilizer (eg, organic acid salt such as sodium citrate, monosaccharide such as glucose, glucose, fructose, mannitol, etc.), coagulating protein and the like. . A commercially available fibrinogen-based main product is fibrinogen-midori [Midori Cross Co., Ltd.] powder, which contains dried fibrinogen as a coagulant protein and stabilizers such as sodium citrate and glucose, glucose, fructose, and mannitol. And the like monosaccharides are added.

The main ingredient consisting of fibrinogen, for example fibrinogen-midori, is water for use, such as distilled water for injection,
It is dissolved in a low salt concentration buffer solution having a pH of 6 to 7. As this low salt concentration buffer solution, 0.01 to 0.03 molar citrate buffer solution is suitable. The melting temperature is preferably 32 to 36 ° C., and it is preferable to maintain the reduced pressure state in the bottle containing fibrinogen during the melting. Under such dissolution conditions, the dry fibrinogen powder dissolves in the range of about 1-10 w / v%.

Further, in the present invention, thrombin, an inhibitor of a fibrinolytic enzyme or a calcium salt can be used as an auxiliary agent.

In the present invention, aprotinin and the like are exemplified as the inhibitor of the fibrinolytic enzyme that constitutes the auxiliary agent. The calcium salt is not particularly limited as long as it is dissociated into calcium ions in an aqueous solution, and examples thereof include calcium chloride.

Further, if necessary, antibiotics, antibacterial agents, anti-inflammatory agents, hemostatic agents and the like may be added.

The subject to be treated in the present invention is abnormal rupture, but the subject to be particularly treated in the present invention is abnormal rupture that is healed by joining the fetal rupture site, and therefore, is generally prior to normal rupture. Abnormal rupture of water,
For example, it is useful for the treatment of early rupture and early rupture.

The method for administering the therapeutic agent for abnormal water rupture in the present invention is usually as follows. That is, the aqueous solution of the main agent composed of fibrinogen prepared as described above is locally injected depending on the application site. When using an auxiliary agent, thrombin following administration of the main agent or simultaneously with the main agent,
An inhibitor of a fibrinolytic enzyme or an adjuvant consisting of calcium salt is injected at the application site. In the case of simultaneous administration of the main agent and the auxiliary agent, the auxiliary agent may be added to the fibrinogen solution in advance.

The dose is 1 to 5 w / v% fibrinogen solution 1 to 5
It is about ml. When an auxiliary agent is used, the auxiliary agent is usually used in the same amount. Here, the respective activities of the auxiliary agents are thrombin 1 to 100 μ / ml, aprotinin 100 to 5000 KIE / m.
l, calcium salt 10-100 mM. 48 doses
The time interval is, for example, about 5 to 10 times.

[Action / effect]

The agent for treating abnormal rupture of water of the present invention is obtained by administering a main agent composed of fibrinogen to a ruptured part of a fetal fossa, and, if necessary, supplemented with thrombin, an inhibitor of a fibrinolytic enzyme and a calcium salt after administration of the main agent. Or by simultaneously administering the above-mentioned main agent and auxiliary agent, the fibrinogen is converted into fibrin, and the fibrin thus produced exerts a bonding action as "paste" to strongly bond the ruptured portion and abnormally rupture the water. Is to treat.

Therefore, the agent for treating abnormal water rupture of the present invention has a very effective therapeutic effect for abnormal water rupture by a simple operation.

[Examples / clinical examples]

Example 1 Sodium citrate and glucose were added as stabilizers to an aqueous solution containing human fibrinogen obtained from corn ethanol fraction I, subjected to sterilization filtration and ultraviolet irradiation, and then aliquoted into bottles and freeze-dried. A fibrinogen preparation containing 1 g of dry medical fibrinogen, 600 mg of sodium citrate, and 1600 mg of glucose in one bottle is obtained.

At the time of use, 50 ml of Japanese Pharmacopoeia distilled water for injection was injected into the bottle containing this fibrinogen formulation with a syringe to maintain the reduced pressure inside the bottle, and the bottle was heated to 32 to 36 ° C and shaken for about 20 minutes, A viscous, clear fibrinogen solution is prepared and transferred into a syringe for topical administration.

Clinical example 1 There are 11 patients with abnormal rupture of water.

For these patients, 2 ml of a 2% fibrinogen solution prepared according to Example 1 was locally applied to the fetal follicle causing rupture.
When the drug was administered 5 to 10 times at 8-hour intervals, a therapeutic effect was observed in 8 cases (remarkably excellent in 2 cases and effective in 6 cases).

Claims (1)

(57) [Claims] 1. A therapeutic agent for abnormal water rupture containing fibrinogen as an active ingredient.