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WO2004091635A1 - Remede pour endometriose et maladies gynecologiques - Google Patents

Remede pour endometriose et maladies gynecologiques Download PDF

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Publication number
WO2004091635A1
WO2004091635A1 PCT/JP2004/005326 JP2004005326W WO2004091635A1 WO 2004091635 A1 WO2004091635 A1 WO 2004091635A1 JP 2004005326 W JP2004005326 W JP 2004005326W WO 2004091635 A1 WO2004091635 A1 WO 2004091635A1
Authority
WO
WIPO (PCT)
Prior art keywords
lactic acid
points
endometriosis
cyclic
poly
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.)
Ceased
Application number
PCT/JP2004/005326
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English (en)
Japanese (ja)
Inventor
Hideaki Tomotsune
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
YUUKO ENTERPRISE CO Ltd
Original Assignee
YUUKO ENTERPRISE CO Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by YUUKO ENTERPRISE CO Ltd filed Critical YUUKO ENTERPRISE CO Ltd
Publication of WO2004091635A1 publication Critical patent/WO2004091635A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics

Definitions

  • the present invention relates to a therapeutic agent for gynecologic diseases suitable for gynecological disorders such as eclampsia, and in particular to a therapeutic agent for gynecological diseases with few side effects when taken.
  • Endometriosis is thought to occur because menstrual blood regurgitation etc. cause endometrial cells to occur in places other than eclampsia. External endometriosis is likely to cause hemorrhage and adhesion of cells in the pelvic cavity, resulting in poor blood circulation, resulting in various symptoms such as pain, menopausal symptoms, constipation and stiff shoulders. Ru.
  • Intrinsic factor deletion of artificial chemical detoxification enzyme gene, deletion of tumor suppressor gene
  • Endometriosis is a disease that is very difficult to cure, and treatments include surgery and medication.
  • patients who wish to become pregnant may have surgery to remove only the lesions and leave the ovaries, but abnormal cells often adhere to surrounding cells and the number of patients after surgery
  • Medications include: 1. pseudo-menopausal and 2. pseudo-pregnancy. Medications used in any of these treatments are designed to temporarily stop menstruation and thereby prevent or reduce endometriosis.
  • G n R H antagonists examples include G n R H antagonists, danazol, medium dose pills, low dose pills and the like.
  • G n R H antagonists are agents that suppress the progression of endometriosis by suppressing ovarian function.
  • Danazol is a therapeutic drug that directly acts on a lesion of eclampsia.
  • a pill is a drug generally used for contraceptive purposes, ovulation and the endodontic membrane It may also be used for the purpose of suppressing the progression of ectocervical intima, since it suppresses the growth of (Refer to Japanese Patent Application Laid-Open No. 10 0 3 6 3 3 (claims 1 and 2 6).
  • the drugs used for either therapy have large side effects and impose a large burden on patients.
  • the G 'n RH antagost creates a low estrogenic state to create a pseudo-menopausal state. Symptoms similar to menopausal disorders such as dizziness and side effects such as bone loss are seen.
  • Danazol is associated with strong side effects such as liver dysfunction and thrombosis, and effects such as weight gain and changes in voice.
  • Medium-dose pills have side effects such as thrombosis, nausea, headache, weight gain, and breast swelling. The low dose pills are not as serious side effects as the medium dose pills, but similar symptoms are recognized.
  • the present invention was made focusing on the above-mentioned points, and an object of the present invention is to provide a therapeutic drug for gynecological diseases with few side effects.
  • Another object of the present invention is to provide a remedy for ectocervical endocarditis with few side effects.
  • the therapeutic agent for gynecological diseases of the present invention is obtained by dehydrating condensation of L-lactic acid by reducing pressure and raising temperature in a nitrogen gas atmosphere, cyclic and / or / or It contains a linear poly L-lactic acid mixture as an active ingredient.
  • cyclic and / or linear poly L monolactic acid mixture is a compound obtained by heat condensation of L mono lactic acid
  • general formula of the cyclic poly L monolactic acid compound is The general formula of the linear poly L monolactic acid compound is shown in Formula 2, respectively. Note that z in the equations 1 and 2 is the degree of condensation. [Formula 1]
  • gynecological diseases women-specific diseases such as dysmenorrhea, menstrual abnormalities, eclampsia, ectopic myoma, ovarian cyst, endometriosis, breast cancer, ectopic cancer, ovarian cancer, etc., symptoms of these diseases and treatment Side effects, and also include menopausal disorders, anemia, coldness, etc. that are particularly manifested in women due to the effects of female hormones, etc.
  • gynecological diseases by enhancing the body's immune system.
  • a drug for treating gynecological diseases that can alleviate the symptoms of gynecological diseases.
  • the gynecological diseases may be endometriosis.
  • the endometrial cell thickening can be suppressed by inhibiting the energy production of the ectocervical cells that have grown outside the eclampsia, and the treatment itself has no side effects.
  • An endometriosis drug is obtained.
  • this therapeutic agent also has the function of regulating the immune system of the body, which alleviates accompanying symptoms such as abdominal pain and back pain.
  • the therapeutic agent for gynecological diseases of the present invention is effective in cyclic and Z- or linear poly-L-lactic acid mixtures obtained by dehydration condensation of L-monolactic acid in a nitrogen gas atmosphere by stepwise depressurization and temperature elevation. It is contained as a component.
  • the therapeutic agent for gynecological diseases may contain 80% by weight or more of a mixture of cyclic and Z- or linear poly-L-lactic acid as an active ingredient.
  • a therapeutic agent for gynecological diseases having a high content of the active ingredient in the intake of the therapeutic agent per dose can be obtained, and a sufficient amount of the active ingredient can be ingested even with a small intake.
  • the therapeutic agent for gynecological disorders is one containing a cyclic and Z- or linear poly-L-lactic acid mixture at 400 mg or more in a daily dose. It is also good.
  • the daily intake of the therapeutic agent for gynecological disorders contains a sufficient amount of cyclic and / or linear poly L-lactic acid mixture, the effect on gynecological disorders is obtained. Is obtained.
  • the cyclic and / or linear poly (L-L-lactic acid) mixture contained as an active ingredient of a gynecological disorder therapeutic agent has a condensation degree in the range of 3 to 19 May be
  • the active ingredient for treating gynecological diseases includes a fraction having a particularly high antitumor effect among cyclic and Z or linear poly L-lactic acid mixtures. It is possible to obtain a gynecological drug with high efficacy.
  • FIG. 1 is a table (No. 1) showing the results for each symptom of this drug administration test.
  • FIG. 2 is a table (No. 2) showing the results for each symptom of the present therapeutic drug administration test.
  • FIG. 3 is a graph showing the transition of the total score for each symptom.
  • FIG. 4 is a graph showing the transition of the total score of all symptoms.
  • the therapeutic agent for gynecological disorders according to the present invention can be obtained by dehydrating condensation of L-lactic acid in a nitrogen gas atmosphere by reducing pressure and raising temperature.
  • it contains a linear poly-L-lactic acid mixture as an active ingredient.
  • a therapeutic agent for gynecological diseases which has the effect of enhancing the immunity of the body and has no side effects is realized.
  • it has the effect of suppressing the thickening of ectocervical intima cells and the effect of enhancing immunity, and is a therapeutic agent for gynecological diseases suitable for the treatment of endometriosis.
  • the poly (L-lactic acid) lactic acid used as an active ingredient of a gynecological disorder therapeutic agent in the present invention has an effect on various diseases, and in particular, has a remarkable effect on various cancers. It has been confirmed as a result of biological experiments that poly L-lactic acid has an effect of promoting apoptosis of malignant cells such as cancer, an effect of acting as a regulator of various phenomena in vivo, and a remarkable sedative effect.
  • Poly L-lactic acid has a remarkable effect on cancer because (1) it inhibits the energy production of cancer cells and drives it to self-destruction, (2) the medical condition improves by improving the body's immune system. It is speculated that it is due to We note that endometriosis is caused by proliferation of dysmorphic cells as well as cancer, and poly L-lactic acid has a remarkable effect on cancer. 4 005326
  • cytokine is a trace chemical substance that regulates cell proliferation, division, and apoptosis, and the environment in the peritoneal cavity is getting worse.
  • prostaglandins one of the causes of pain, are increased, while non-K cells, which control the body's immune system and suppress the growth of lesions, are decreasing.
  • poly-L-lactic acid relieves symptoms by regulating immune function by preventing vagus or runaway of physiologically active substances such as cytokines.
  • Oxygen dissociation is thought to involve 2-3 PG BPG (2 ⁇ ⁇ 3-bisphosglyceric acid), but poly-L-lactic acid promotes the addition of this substance, and it also induces the transformation of poly-L-lactic acid in red blood cells.
  • Noble size of blood vessel is matched to size of red blood cell, size adjustment ability to smooth blood flow
  • Poly (L-L-lactic acid) is obtained by dehydrating and condensing L- (L-lactic acid) stepwise in nitrogen gas atmosphere and dehydrating condensation, and it has cyclicity with various condensation degree depending on conditions such as heating temperature and heating time. And Z or a linear poly L monolactic acid mixture is obtained.
  • the poly-L-monolactic acid mixture is obtained in a mixed state of a cyclic poly-L-monolactic acid compound and a linear poly-L-monolactic acid compound.
  • the degree of condensation is not particularly limited, but it is desirable to contain a mixture of poly-L-lactic acid with a degree of condensation of 1 to 19 having a high antitumor effect, and a mixture of poly-L-lactic acid of degree of condensation of 5 to 14 is also included. It is better if you As mentioned above, endometriosis is caused by proliferation of atypical cells as well as cancer, so fractions with high degree of condensation of 15 to 19 in antitumor effect, 5 to 14 in degree of condensation Fractions are also expected to have a high effect on endometriosis.
  • the cyclic and / or linear poly-L-lactic acid mixture obtained by the above-mentioned procedure may be used as it is as a therapeutic agent for oral intake.
  • You may add sweeteners such as milk and trehalose, fortifying agents such as calcium lactate, flavors and preservatives.
  • excipients, pinders, etc. may be added to form tablets, or may be packed into capsules.
  • the dosage per one administration of the therapeutic agent for gynecological disorders according to the present invention is about 2 to 6 g, and it is desirable that the dosage per day be about 2 to 3 times. . Too much per dose, or too many doses per day, can be painful for the user to take the treatment, which is less preferable.
  • the cyclic and / or linear mixture of poly (L-L-lactic acid) be contained in an amount of 4800 mg or more in a daily dose. If the daily therapeutic drug intake is too low, the effects of the gynecological disorder therapeutics may not be sufficiently obtained.
  • a therapeutic agent for endometriosis and gynecological diseases can be obtained.
  • Test subjects Patients with ectopic eclampsia endometriosis 10 (ages 22 to 35, average 28. 2). All of them were diagnosed with dysmenorrhea (6 persons with severe symptoms, 4 persons with moderate symptoms) without any prior surgery and have not received any particular treatment.
  • FIG. 1 shows “menstrual pain”, “lower abdominal pain other than menstrual pain”, “back pain other than menstrual pain”, “pelvic pain and discomfort, hip discomfort”, “anal pain ⁇ push up at the time of sitting”
  • the results of evaluation of the symptoms of “intercourse pain” and “overweight / overlong menstruation” are shown in FIG. 2 for “lever-like 'membranous clot”,' corruption bleeding ',' anemia, dizziness', 'fever',
  • the evaluation results of “nausea, vomiting”, “stiff shoulder, head weight, headache” and “chilliness (especially in the lower extremities)” are shown.
  • FIG. 3 The graph showing the transition of the total score for each symptom in the administration test results is shown in Fig. 3 and the graph showing the transition of the total score of all symptoms is shown in Fig. 4c .
  • the longer the administration period for any symptom the more the symptom tends to be reduced to disappear, and it can be seen that the graph is in the lower right shoulder.
  • the total score decreases as the administration period becomes longer, and the overall improvement is achieved.
  • Figures 1 to 4 are numerical values of the subject's own thoughts, The clinical findings also show improvement results.
  • changes in post-trial changes also showed a tendency for improvement in parallel to the symptoms after changes in the condition of the capsule fossa by internal examination and the condition of the focus area by image diagnosis. For various other symptoms, some degree of relief or disappearance was observed after the trial. In addition, after administration of this drug, no side effects such as those of conventional drugs were observed, and no abnormal values were observed in clinical laboratory data.
  • this drug has two reasons: (1) it inhibits the energy production of cancer cells and drives them to self-destruction; (2) it improves the medical condition by improving the body's immune system; It is presumed to be effective against endometriosis and gynecological diseases. However, visible “improvement of immunity” does not occur in a short period, and ectocarditis itself is also time-consuming to cure, and drug administration and observation are carried out for a long period of time. It is presumed that a clear effect can be found by this.
  • the therapeutic agent for gynecological diseases can alleviate general gynecological diseases and various symptoms thereof by enhancing the immunity of the body. In addition, since it has no side effects like common therapeutic agents, it can be used freely even in mild cases.
  • the therapeutic agent for endometriosis according to the present invention can suppress thickening of the intimal cell of the eclampsia by inhibiting the energy production of the intimal cell of the ectopically grown in other places than the uterus.
  • the body's immune system by adjusting the body's immune system, accompanying symptoms such as abdominal pain and back pain are alleviated and there are no side effects.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention se rapporte à un remède pour maladies gynécologiques, qui présente peu d'effets secondaires. L'invention concerne un remède pour maladies gynécologiques qui se caractérise en ce qu'il contient, en tant que principe actif, un mélange d'acides poly-L-lactiques cycliques et/ou linéaires que l'on obtient en chauffant de l'acide L-lactique dans une atmosphère contenant de l'azote gazeux, sous une pression réduite, afin de déshydrater et de condenser ledit acide.
PCT/JP2004/005326 2003-04-14 2004-04-14 Remede pour endometriose et maladies gynecologiques Ceased WO2004091635A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2003-109507 2003-04-14
JP2003109507A JP2004175783A (ja) 2003-04-14 2003-04-14 子宮内膜症及び婦人科疾患の治療薬

Publications (1)

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WO2004091635A1 true WO2004091635A1 (fr) 2004-10-28

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PCT/JP2004/005326 Ceased WO2004091635A1 (fr) 2003-04-14 2004-04-14 Remede pour endometriose et maladies gynecologiques

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JP (1) JP2004175783A (fr)
KR (1) KR20060002708A (fr)
WO (1) WO2004091635A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102037448B1 (ko) 2017-11-21 2019-10-28 경희대학교 산학협력단 데하이드로코스투스 락톤을 포함하는 자궁세포 이상증식 질환의 예방, 개선 또는 치료용 조성물

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05310581A (ja) * 1992-05-15 1993-11-22 Koken Kk 人を含む動物の悪性腫瘍細胞増殖抑制剤
JPH06336427A (ja) * 1993-05-26 1994-12-06 Global Art Kk 人を含む動物の悪性腫瘍細胞増殖抑制剤
JPH09227388A (ja) * 1996-02-15 1997-09-02 Naganushi Tetsuaki 大腸癌、食道癌及び乳癌より選ばれた癌に用いる抗悪性腫瘍剤
JPH10130153A (ja) * 1996-10-28 1998-05-19 Shiyumeidou:Kk 大腸癌、食道癌及び乳癌より選ばれた癌に用いる 抗悪性腫瘍剤
JP2001139476A (ja) * 1999-11-15 2001-05-22 Youichirou Naganushi 癌を含めた悪性新生物に用いる抗悪性腫瘍剤
WO2001054705A1 (fr) * 2000-01-26 2001-08-02 Amato Pharmaceutical Products, Ltd. Inhibiteurs d'implantation de cellules cancereuses
WO2002060457A1 (fr) * 2001-01-24 2002-08-08 Amato Pharmaceutical Products,Ltd. Agents anti-stress
JP2002356433A (ja) * 2001-05-30 2002-12-13 Tendou Seiyaku Kk 免疫賦活剤
WO2003007937A1 (fr) * 2001-07-18 2003-01-30 Amato Pharmaceutical Products, Ltd. Agent antitumoral contenant de l'acide polylactique cyclique
WO2003039560A1 (fr) * 2001-11-06 2003-05-15 Amato Pharmaceutical Products, Ltd. Agent antitumoral contenant un melange d'oligomeres d'acide lactique
JP2004155670A (ja) * 2002-11-01 2004-06-03 Youichirou Naganushi 細胞賦活剤、細胞賦活剤製造方法及びその装置

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05310581A (ja) * 1992-05-15 1993-11-22 Koken Kk 人を含む動物の悪性腫瘍細胞増殖抑制剤
JPH06336427A (ja) * 1993-05-26 1994-12-06 Global Art Kk 人を含む動物の悪性腫瘍細胞増殖抑制剤
JPH09227388A (ja) * 1996-02-15 1997-09-02 Naganushi Tetsuaki 大腸癌、食道癌及び乳癌より選ばれた癌に用いる抗悪性腫瘍剤
JPH10130153A (ja) * 1996-10-28 1998-05-19 Shiyumeidou:Kk 大腸癌、食道癌及び乳癌より選ばれた癌に用いる 抗悪性腫瘍剤
JP2001139476A (ja) * 1999-11-15 2001-05-22 Youichirou Naganushi 癌を含めた悪性新生物に用いる抗悪性腫瘍剤
WO2001054705A1 (fr) * 2000-01-26 2001-08-02 Amato Pharmaceutical Products, Ltd. Inhibiteurs d'implantation de cellules cancereuses
WO2002060457A1 (fr) * 2001-01-24 2002-08-08 Amato Pharmaceutical Products,Ltd. Agents anti-stress
JP2002356433A (ja) * 2001-05-30 2002-12-13 Tendou Seiyaku Kk 免疫賦活剤
WO2003007937A1 (fr) * 2001-07-18 2003-01-30 Amato Pharmaceutical Products, Ltd. Agent antitumoral contenant de l'acide polylactique cyclique
WO2003039560A1 (fr) * 2001-11-06 2003-05-15 Amato Pharmaceutical Products, Ltd. Agent antitumoral contenant un melange d'oligomeres d'acide lactique
JP2004155670A (ja) * 2002-11-01 2004-06-03 Youichirou Naganushi 細胞賦活剤、細胞賦活剤製造方法及びその装置

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Publication number Publication date
JP2004175783A (ja) 2004-06-24
KR20060002708A (ko) 2006-01-09

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