CN113967249A - Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression - Google Patents
Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression Download PDFInfo
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- CN113967249A CN113967249A CN202111513676.7A CN202111513676A CN113967249A CN 113967249 A CN113967249 A CN 113967249A CN 202111513676 A CN202111513676 A CN 202111513676A CN 113967249 A CN113967249 A CN 113967249A
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- parathyroid hormone
- depression
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- pharmaceutical composition
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone (parathormone); Parathyroid hormone-related peptides
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- 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
- A61P25/24—Antidepressants
Abstract
The invention provides an application of parathyroid hormone, such as recombinant human parathyroid hormone (1-34) or parathyroid hormone-related protein, in preparing a medicament or health product for treating male depression. The invention discovers for the first time that parathyroid hormone has the probability of causing depression in women, but has opposite effects in men, and can improve the organism metabolism and activity of men, thereby improving the behavior related to depression of men.
Description
Technical Field
The invention belongs to the technical field of depression treatment medicines, and relates to application of parathyroid hormone in preparation of a medicine or a health-care product for treating male depression.
Background
Depression is also called as depressive disorder, and clinically, depression is caused by low mood, thought retardation, active speech reduction, slow behavior, passive life, unwillingness of contact with people, easy lacrimation and crying, obvious anxiety and motility are caused in some cases, and psychogenic symptoms such as hallucinations, delusions and the like can appear in serious cases. With the acceleration of life rhythm and the increase of life and working pressure, depression becomes a common disease affecting human health, is a disease with higher morbidity, disability rate and fatality rate, and seriously harms physical and psychological health of people. Therefore, depression has become a hot spot of research in the medical field today. Postpartum melancholia, senile depression, depression caused by medicines or diseases, endogenous depression and the like are common, and psychological counseling, medication and the like are common treatment means, but the cause of disease is complex, and the effect is not ideal.
Parathyroid hormone (PTH) is an important hormone regulating calcium and phosphorus metabolism in the body. The main role of PTH in the body is to maintain calcium homeostasis in the blood by regulating tubular resorption and mobilizing bone cell function. Clinically, parathyroid hormone-related disorders are commonly associated with neurological symptoms, from which the effects of PTH on the central nervous system can be seen.
The recombinant human parathyroid hormone (1-34) is internationally applied to clinically treating osteoporosis of old men and postmenopausal women. Depression and osteoporosis are multiple diseases in elderly men and postmenopausal women. Previous studies have indicated that: osteoporosis and the onset of depression are correlated in elderly men and postmenopausal women.
Disclosure of Invention
In view of the defects of the prior art, the technical problem to be solved by the invention is to provide the application of the parathyroid hormone in preparing the medicine or health care product for treating male depression so as to improve the male depression symptoms.
In order to realize the purpose, the invention provides an application of parathyroid hormone in preparing a medicament or a health-care product for treating male depression.
Specifically, the parathyroid hormone is recombinant human parathyroid hormone (1-34) or parathyroid hormone-related protein.
Another aspect of the present invention is to provide a pharmaceutical composition or health product for treating male depression, which contains parathyroid hormone or a pharmaceutically acceptable salt thereof as an active substance.
Specifically, the parathyroid hormone is recombinant human parathyroid hormone (1-34) or parathyroid hormone-related protein.
Specifically, the pharmaceutical composition is in an intravenous injection administration form and an oral administration form.
Specifically, the administration dose of the pharmaceutical composition is 300 ng/kg-500 ng/kg once a day.
Specifically, the pharmaceutical composition is administered between 2 and 5 pm daily.
The parathyroid hormone provided by the embodiment of the invention is applied to the preparation of a medicine or health care product for treating male depression, and particularly the parathyroid hormone is used as an active substance of the medicine or health care product for treating male depression. Parathyroid hormone can improve metabolism and activity of male organism, so that male depression-related behavior can be improved, and male depression symptoms can be improved.
Drawings
FIGS. 1 to 3 are graphs showing the statistical results of the open field experiment performed on experimental male rats in example 1 of the present invention;
FIG. 4 is a graphical representation of the statistical results of a sugar water preference test conducted on experimental male rats in example 2 of the present invention;
FIGS. 5 to 7 are graphs showing the statistical results of the open field experiment performed on experimental male rats in example 3 of the present invention;
FIGS. 8 to 10 are graphs showing the statistical results of the open field experiment performed on experimental male rats in example 4 of the present invention;
FIG. 11 is a graphical representation of the statistical results of a sugar water preference test conducted on experimental male rats in example 5 of the present invention;
FIGS. 12 to 14 are graphs showing the statistical results of the open field experiments conducted on the female rats in the experiment of example 6;
FIG. 15 is a graph showing the statistical results of the tail suspension experiment performed on real female mice in example 6 of the present invention;
FIGS. 16 to 18 are graphs showing the statistical results of open field experiments conducted on experimental female rats in example 7 of the present invention;
FIG. 19 is a graph showing the statistical results of the tail suspension experiment performed on the real female mouse in example 7 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention are described in detail below with reference to the accompanying drawings. Examples of these preferred embodiments are illustrated in the accompanying drawings. The embodiments of the invention shown in the drawings and described in accordance with the drawings are exemplary only, and the invention is not limited to these embodiments.
It should be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and/or processing steps closely related to the scheme according to the present invention are shown in the drawings, and other details not so relevant to the present invention are omitted.
As described above, although clinical treatment means for depression generally include psychological counseling, drug therapy, and the like, since the cause of disease is complex and the effect is not ideal, the search for therapeutic drugs for depression is still a hot spot in research in the medical field of today. The invention discovers for the first time that parathyroid hormone has the probability of causing depression in women, but has opposite effects in men, and can improve the organism metabolism and activity of men, thereby improving the behavior related to depression of men.
Based on the above findings, the embodiments of the present invention first provide an application of parathyroid hormone in the preparation of a drug or a health product for treating male depression. Specifically, the parathyroid hormone is recombinant human parathyroid hormone (1-34), namely rPTH (1-34), or parathyroid hormone-related protein PTHrP.
The embodiment of the invention also provides a medicine or health-care product for treating male depression, wherein the medicine composition or the health-care product contains parathyroid hormone or pharmaceutically acceptable salt thereof as an active substance. Specifically, the parathyroid hormone is recombinant human parathyroid hormone (1-34), namely rPTH (1-34), or parathyroid hormone-related protein PTHrP.
In a preferred embodiment, the pharmaceutical composition is in the form of intravenous injection or oral administration.
In a preferred embodiment, the pharmaceutical composition is administered once daily at a dose of 300ng/kg to 500ng/kg, for example 300ng/kg, 310ng/kg, 330ng/kg, 350ng/kg, 380ng/kg, 400ng/kg, 420ng/kg, 450ng/kg, 480ng/kg or 500 ng/kg. The continuous medication time is no more than two years.
In a preferred embodiment, the pharmaceutical composition is administered between 2 and 5 pm daily.
In order to show that the medicine or health product for treating male depression provided by the invention can be used for relevant clinical research, the embodiment of the invention provides a pharmacodynamic embodiment of a C57 mouse.
Example 1
Ordinary adult C57 males were selected and randomly divided into two groups: one group was the administration group, and one group was the control group.
(1) And C57 male mice of the administration group and the control group are respectively administered according to the following modes:
administration group: the rPTH (1-34) was intraperitoneally injected over a period of 2-5 p.m. at a dose of 10ng/30g (333 ng/kg).
Control group: the difference from the administered group was only that the control group was injected with the same dose of physiological saline.
(2) After the administration, the open field experiment is carried out on the male mice of the administration group and the control group respectively, and the open field center residence time (central times), the open field center entering times (central entries) and the overall activity Distance (Distance) of the two groups of male mice are recorded and counted.
Fig. 1 is a graph showing the statistical result of the residence time at the center of the open field of two groups of male rats in this embodiment, fig. 2 is a graph showing the statistical result of the number of times of entry into the center of the open field of two groups of male rats in this embodiment, and fig. 3 is a graph showing the statistical result of the overall movement distance of two groups of male rats in this embodiment.
As shown in fig. 1 to 3, the above experimental results show that: compared with the control group, the open field center residence time, the open field center entry times and the overall movement distance of the male mice in the administration group are all significantly increased, that is, the movement amount of the male mice is significantly increased after administration.
Example 2
Ordinary adult C57 males were selected and randomly divided into two groups: one group was the administration group, and one group was the control group.
(1) And C57 male mice of the administration group and the control group are respectively administered according to the following modes:
administration group: the rPTH (1-34) was intraperitoneally injected over a period of 2-5 p.m. at a dose of 10ng/30 g.
Control group: the difference from the administered group was only that the control group was injected with the same dose of physiological saline.
(2) After the administration, the sugar water preference experiment is carried out on the male mice of the administration group and the control group, and the sugar water preference ratio (ratio/water) of the two groups of male mice is recorded and counted.
FIG. 4 is a graphical representation of the statistics of the sugar water preference ratios of the two groups of male rats in this example.
As shown in fig. 4, the above experimental results show that: the carbohydrate water preference of the male mice of the administered group was significantly increased compared to the control group.
Example 3
Ordinary adult C57 males were selected and randomly divided into two groups: one group was a depressed group and one group was a control group.
(1) Performing depression molding on C57 male mice in a depression group for 10 days, and causing animal stress depression through a constraint model; the male rats in the control group were not subjected to depression molding treatment.
(2) And after the depression modeling is finished, performing open field experiments on the male rats of the depression group and the male rats of the control group respectively, and recording and counting the open field center residence time, the open field center entering times and the whole moving distance of the two groups of male rats.
Fig. 5 is a graph showing the statistical result of the residence time at the center of the open field of two groups of male rats in the present embodiment, fig. 6 is a graph showing the statistical result of the number of times of entry at the center of the open field of two groups of male rats in the present embodiment, and fig. 7 is a graph showing the statistical result of the overall movement distance of two groups of male rats in the present embodiment.
As shown in fig. 5 to 7, the above experimental results show that: compared with the control group, the open field center residence time and the open field center entering frequency of the male rat in the depressed group are reduced, and the whole activity distance is obviously reduced, namely, the activity of the male rat is obviously reduced, and the male rat has the characteristic of stress depression.
Example 4
C57 male rats were modeled after 10 days of depression by treatment of the depressed group in example 3 from normal adult C57 male rats and then randomized into two groups: one group was the administration group, and one group was the control group.
(1) And C57 male mice of the administration group and the control group are respectively administered according to the following modes:
administration group: the rPTH (1-34) was intraperitoneally injected over a period of 2-5 p.m. at a dose of 10ng/30 g.
Control group: the difference from the administered group was only that the control group was injected with the same dose of physiological saline.
(2) After dosing, the male rats of the dosing group and the control group are subjected to open field experiments respectively, and the open field center residence time, the open field center entering times and the whole moving distance of the two groups of male rats are recorded and counted.
Fig. 8 is a graph showing the statistical result of the residence time at the center of the open field of two groups of male rats in the present embodiment, fig. 9 is a graph showing the statistical result of the number of times of entry at the center of the open field of two groups of male rats in the present embodiment, and fig. 10 is a graph showing the statistical result of the overall movement distance of two groups of male rats in the present embodiment.
As shown in fig. 8 to 10, the above experimental results show that: compared with the control group, the open field center residence time, the open field center entering times and the whole moving distance of the male mice of the administration group are obviously increased, namely, after the administration, the activity of the male mice is obviously increased, and the symptoms of the pressure stress depression are improved.
Example 5
(1) The administration method was the same as in example 4, except that C57 males were obtained in the administration group and the control group.
(2) And after the administration is finished, respectively carrying out a sugar water preference experiment on the male mice of the administration group and the control group, and recording and counting the sugar water preference proportion of the two groups of male mice.
FIG. 11 is a graphical representation of the statistics of the sugar water preference ratios of the two groups of male rats in this example.
As in fig. 11, the above experimental results show that: for male mice with symptoms of stress-stress depression, the carbohydrate water preference of the male mice of the administered group was significantly increased compared to the control group.
Example 6
This example is compared with example 1 except that the test subjects were replaced with female mice, that is, ordinary adult C57 female mice were taken and the test was performed in the same manner as in example 1.
Fig. 12 is a graph showing the statistical result of the open field center residence time of the two groups of female rats in this example, fig. 13 is a graph showing the statistical result of the number of times of entry into the open field center of the two groups of female rats in this example, and fig. 14 is a graph showing the statistical result of the overall movement distance of the two groups of female rats in this example.
As shown in fig. 12 to 14, the above experimental results show that: the open field center residence time, open field center entry times and overall movement distance of the normal adult female C57 mice were about the same as those of the administration group and the control group, and were not significantly changed.
In this example, female mice in the administration group and the control group were subjected to tail suspension test, and the time of tail suspension immobility (immility) was recorded.
FIG. 15 is a graph showing the statistics of the time of tail suspension immobility of two groups of female mice in this example.
As in fig. 15, the above experimental results show that: compared with the control group, the time of tail suspension immobility of the female mice of the administration group is increased, but the difference is not large.
Example 7
This example is different from example 6 in that the test subjects were replaced with female mice whose ovaries were removed for 4 weeks, that is, C57 female mice of an average adult were taken and ovaries were removed for 4 weeks, and then the test was performed in the same manner as in example 6.
Fig. 16 is a graph showing the statistical result of the open field center residence time of two groups of female rats in the present example, fig. 17 is a graph showing the statistical result of the number of times of entry into the open field center of two groups of female rats in the present example, fig. 18 is a graph showing the statistical result of the overall movement distance of two groups of female rats in the present example, and fig. 19 is a graph showing the statistical result of the tail suspension immobility time of two groups of female rats in the present example.
As shown in fig. 16 to 19, the above experimental results show that: for female mice after 4 weeks of ovariectomy, the open-field center residence time, the open-field center entry times and the overall movement distance of the female mice of the administration group were significantly reduced, while the tail suspension immobility time was significantly increased, compared to the control group.
The experimental results of the above examples 1 to 5 show that: the injection administration of the parathyroid hormone can promote the activity of the male animal body, obviously increase the preference of sugar water, and has the effect of relieving depression-related symptoms such as activity reduction, sugar water preference reduction and the like caused by long-term pressure stress, namely, the parathyroid hormone can improve the body metabolism and activity of the male and can play a role in improving the male depression symptoms.
Examples 6 and 7 show that administration by injection of parathyroid hormone reduces the body activity of females, i.e., parathyroid hormone has a chance to cause depression in females.
The foregoing is directed to embodiments of the present application and it is noted that numerous modifications and adaptations may be made by those skilled in the art without departing from the principles of the present application and are intended to be within the scope of the present application.
Claims (7)
1. Application of parathyroid hormone in preparing medicine or health product for treating male depression is provided.
2. The use of claim 1, wherein the parathyroid hormone is recombinant human parathyroid hormone (1-34) or parathyroid hormone-related protein.
3. A medicament or health product for treating male depression, which comprises parathyroid hormone or a pharmaceutically acceptable salt thereof as an active substance.
4. The pharmaceutical composition or health product according to claim 3, wherein the parathyroid hormone is recombinant human parathyroid hormone (1-34) or parathyroid hormone-related protein.
5. The pharmaceutical composition or health product according to claim 4, wherein the pharmaceutical composition is in the form of intravenous injection or oral administration.
6. The pharmaceutical composition or health product according to claim 5, wherein the pharmaceutical composition is administered once daily at a dose of 300ng/kg to 500ng/kg per time.
7. The pharmaceutical composition or health product according to claim 6, wherein the pharmaceutical composition is administered between 2 and 5 pm daily.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111513676.7A CN113967249A (en) | 2021-12-10 | 2021-12-10 | Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression |
| PCT/CN2021/137974 WO2023102970A1 (en) | 2021-12-10 | 2021-12-14 | Use of parathyroid hormone in preparation of drug or health care product for treating male depression |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111513676.7A CN113967249A (en) | 2021-12-10 | 2021-12-10 | Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression |
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| CN113967249A true CN113967249A (en) | 2022-01-25 |
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| CN202111513676.7A Pending CN113967249A (en) | 2021-12-10 | 2021-12-10 | Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression |
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| CN (1) | CN113967249A (en) |
| WO (1) | WO2023102970A1 (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281370A (en) * | 1997-12-09 | 2001-01-24 | 伊莱利利公司 | Stabilized teriparatide solutions |
| CN101445486A (en) * | 2002-12-23 | 2009-06-03 | 诺瓦提斯公司 | Derivatives of aryl-quinazoline/aryl-2-amino-phenyl methanone which promote the release of parathyroid hormone |
| CN106309358A (en) * | 2015-06-29 | 2017-01-11 | 成都金凯生物技术有限公司 | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof |
| CN106924721A (en) * | 2015-12-28 | 2017-07-07 | 成都金凯生物技术有限公司 | The pharmaceutical composition containing human parathyroid hormone of direct oral cavity mucosal drug delivery |
| US20190262613A1 (en) * | 2016-11-11 | 2019-08-29 | Galvani Bioelectronics Limited | Treatment of diseases mediated by thyroid and parathyroid hormones |
| CN111529691A (en) * | 2020-06-03 | 2020-08-14 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Use of parathyroid hormone (1-34) in preparing medicine for treating male hypogonadism |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0114701D0 (en) * | 2001-06-15 | 2001-08-08 | Novartis Ag | Organic compounds |
| CN107375910B (en) * | 2017-07-12 | 2020-03-24 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Application of PTHrP in preparation of medicine for treating male hypogonadism syndrome |
-
2021
- 2021-12-10 CN CN202111513676.7A patent/CN113967249A/en active Pending
- 2021-12-14 WO PCT/CN2021/137974 patent/WO2023102970A1/en unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281370A (en) * | 1997-12-09 | 2001-01-24 | 伊莱利利公司 | Stabilized teriparatide solutions |
| CN101445486A (en) * | 2002-12-23 | 2009-06-03 | 诺瓦提斯公司 | Derivatives of aryl-quinazoline/aryl-2-amino-phenyl methanone which promote the release of parathyroid hormone |
| CN106309358A (en) * | 2015-06-29 | 2017-01-11 | 成都金凯生物技术有限公司 | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof |
| CN106924721A (en) * | 2015-12-28 | 2017-07-07 | 成都金凯生物技术有限公司 | The pharmaceutical composition containing human parathyroid hormone of direct oral cavity mucosal drug delivery |
| US20190262613A1 (en) * | 2016-11-11 | 2019-08-29 | Galvani Bioelectronics Limited | Treatment of diseases mediated by thyroid and parathyroid hormones |
| CN111529691A (en) * | 2020-06-03 | 2020-08-14 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Use of parathyroid hormone (1-34) in preparing medicine for treating male hypogonadism |
Non-Patent Citations (2)
| Title |
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| 冷勇敢等: "甲状旁腺素研究进展①", 药物生物技术, vol. 18, no. 3, pages 278 - 282 * |
| 陈煜东等: "甲状旁腺激素结合心理治疗对骨质疏松性椎体压缩骨折患者 骨代谢相关指标和心理健康状况的影响", 中国健康心理学杂志, vol. 26, no. 6, pages 877 - 880 * |
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| WO2023102970A1 (en) | 2023-06-15 |
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