JPH05194239A - Therapeutic agent for hot flash caused by oval deletion - Google Patents

Abstract

PURPOSE:To provide a therapeutic agent for hot flash caused by oval deletion with a reduced dose and no side effect. CONSTITUTION:The objective therapeutic agent for hot flash caused by oval deletion contains an activated-form vitamin D selected from the group consisting of (a) 1alpha-hydroxy vitamin D, (b) 1alpha,24-(R)-dihydroxy vitamin D, (c) 1alpha, 25- dihydroxy vitamin D, (d) 1alpha,24,25-trihydroxy vitamin D, (e) 24,24-difluoro-1alpha,25- dihydroxy vitamin D, (f) 26,26,26,27,27,27-hexafluoro-1alpha, 25-dihydroxy vitamin D, (g) 25-hydroxy vitamin D3-26,23-lactone, (h) 1alpha, 25-dihydroxy vitamin D3-26,23- lactone, preferably a through c, particularly a, as an active ingredient. The active ingredient is usually given 0.01 to 4.0mug/day/man, preferably 0.25 to 2.0mug/day/man, in the oral form of soft capsules, hard capsules, tablets, syrup, in the injection form or external application form.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a therapeutic agent for hot flashes caused by ovarian loss.

[0002]

2. Description of the Related Art Hot flashes due to ovarian loss are believed to be caused by a decrease in female hormones, and are known to occur after ovariectomy or treatment to reduce ovarian function. There is.

Although there are individual differences in the degree of symptoms, it is said that almost 100% of women who have undergone ovariectomy or decreased ovarian function are treated.

The time of onset of symptoms is sudden and unpredictable.
Therefore, the pain caused by the onset is more than the degree of symptoms. Usually, it is said that the more likely it is to be affected by changes in emotions and exertion, the more nervous women tend to become more severe.

Further, hot flashes due to ovarian loss have an illness period of about 2 years, which is a psychological stress that is immeasurable for women. Particularly in modern society, even women are required to have the judgment and execution ability according to the opportunity, just like men because of social needs. For women in this position, physical handicap such as hot flashes due to ovarian loss should be minimized as much as possible.
It can simply be said that it has importance beyond clinical clinical issues.

[0006] Conventional drug therapy includes the administration of female hormone agents and the administration of tranquilizers, each of which has the following problems. The most effective female hormone drug not only increases the risk of developing adenocarcinoma of the uterine uterus, but it is contraindicated in patients with a history of hormone-dependent tumors such as breast cancer. Also, arrhythmia bleeding,
There are also common side effects such as lower abdominal pain and headaches, so they are not always suitable for long-term treatment. In addition to side effects such as drowsiness, tranquilizers do not always have stable effects. From the above, there is a demand for the development of a highly effective therapeutic method with few side effects using an oral agent.

By the way, a woman suffering from hot flashes due to ovarian loss has abnormal calcium metabolism and abnormal vitamin metabolism. Therefore, it is speculated that the occurrence of this symptom may have some influence on the abnormal calcium metabolism and, in turn, the presence of vitamin D, which is closely related thereto.

On the other hand, 1α-hydroxyvitamin D, 1
α, 24- (R) -dihydroxyvitamin D, 1α, 2
Activated vitamin Ds such as 5-dihydroxyvitamin D promote calcium absorption in the small intestine and bone absorption in bone.
It is a well-established therapeutic drug for diseases associated with various abnormalities of calcium metabolism, which has a bone formation regulating effect and the like.

[0009]

Then, the present inventors diligently examined how the active vitamin D affects hot flashes caused by ovarian loss, and as a result, surprisingly, the active vitamin D was found to be high. The inventors of the present invention have reached the present invention by discovering that it has an action of improving hot flashes due to ovarian loss with a very small amount and no side effects. That is, the present invention is an agent for treating hot flashes caused by ovarian deficiency, which contains active vitamin D as an active ingredient.

The active vitamin D in the present invention includes active VD ₂ , active VD ₃ and derivatives thereof, and specific examples thereof include 1α-hydroxyvitamin D, 1α, 24- (R ) -Dihydroxyvitamin D, 1α, 25-dihydroxyvitamin D, 1α,
24,25-trihydroxyvitamin D, 24,24-
Difluoro-1α, 25-dihydroxyvitamin D, 2
6,26,26,27,27,27-hexafluoro-
1α, 25-dihydroxyvitamin D, 25-hydroxyvitamin D ₃ -26,23-lactone, 1α, 25-
Examples thereof include dihydroxyvitamin D ₃ -26,23-lactone. Of these, 1α-hydroxyvitamin D ₃ , 1α, 24- (R) -dihydroxyvitamin D ₃ , and 1α, 25-dihydroxyvitamin D ₃ are preferable, and among these, 1α-hydroxyvitamin D is particularly preferable.
₃ is preferred.

These active ingredients are prepared by a known method using suitable excipients and the like to prepare soft capsules, hard capsules, tablets,
It can be used as an oral preparation such as a syrup, an injection, or an external preparation.

The dose of the active ingredient is usually 0.01 to 4.
0 μg / day / person, preferably 0.25 to 2.0 μ
g / day / person. It is preferable to prepare a formulation that satisfies such conditions.

The method of the present invention can also be used in combination with existing drug therapeutic agents.

The present invention will be described in detail below with reference to examples.

[0015]

[Examples] Hot flashes appeared due to ovarian loss 22
As an example, 0.5 μg / day of 1α-hydroxyvitamin D ₃ , which is active vitamin D ₃ , was orally administered.

By administration for 1 month, the symptoms disappeared or improved in 20 of 22 cases, and the efficacy rate reached 90.9%.

In these symptoms, changes in calcium metabolism before and after oral administration of 1α-hydroxyvitamin D ₃ were examined.

The concentration of ionized calcium in serum was 1.23 ± 0.05 μmol / l in the case of no hot flash and 1.28 μmol / l in the case of high-grade hot flash, which tended to increase as the symptoms became higher. By administration of this drug,
It dropped to 1.26 ± 0.04 μmol / l.

Similarly, the serum calcium concentration is 9.58 ± 0.46 mg / dl in the non-hot flash and 9.98 mg / dl in the high hot flash, which tends to increase as the symptoms increase. By administration of this drug, 9.89 mg /
dropped to dl.

The amount of calcium excreted in urine (creatinine-corrected) was 0.25 without hot flashes and 0.20 with high hot flashes, which tended to decrease as the symptoms became higher. , 0.22 ± 0.13
And rose.

From the above, 1α which is active vitamin D ₃
-Oral administration of hydroxyvitamin D ₃ normalizes abnormalities in calcium metabolism, which are considered to be related to the occurrence of hot flashes, and was found to be effective for 90.9% hot flashes.

Therefore, it can be said that active vitamin D is a very effective therapeutic agent for hot flashes due to ovarian loss, with very small amounts of active vitamin D and no side effects.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Yumiko Kiyomiya 3-12-16 Kamiigusa, Suginami-ku, Tokyo No. 301 Dowel Igusa (72) Inventor Nagatoshi Aoki 2-1-1, Uchisaiwaicho, Chiyoda-ku, Tokyo No Building) Teijin Limited

Claims (2)

[Claims] 1. A hot flash remedy for ovarian deficiency containing active vitamin D as an active ingredient. 2. The active vitamin D is 1α-hydroxyvitamin D, 1α, 24- (R) -dihydroxyvitamin D, 1α, 25-dihydroxyvitamin D, 1α, 2.
4,25-trihydroxyvitamin D, 24,24-difluoro-1α, 25-dihydroxyvitamin D, 2
6,26,26,27,27,27-hexafluoro-
1α, 25-dihydroxyvitamin D, 25-hydroxyvitamin D ₃ -26,23-lactone, 1α, 25-
The hot flash therapeutic agent according to claim 1, which is selected from the group consisting of dihydroxyvitamin D ₃ -26,23-lactone.