WO2024082230A1 - Utilisation d'acétate de desloréline dans la préparation d'un médicament destiné à réguler le cycle sexuel d'un animal - Google Patents
Utilisation d'acétate de desloréline dans la préparation d'un médicament destiné à réguler le cycle sexuel d'un animal Download PDFInfo
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- WO2024082230A1 WO2024082230A1 PCT/CN2022/126514 CN2022126514W WO2024082230A1 WO 2024082230 A1 WO2024082230 A1 WO 2024082230A1 CN 2022126514 W CN2022126514 W CN 2022126514W WO 2024082230 A1 WO2024082230 A1 WO 2024082230A1
- Authority
- WO
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- Prior art keywords
- drug
- acetate
- injection
- animal
- sexual cycle
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 41
- 229940079593 drug Drugs 0.000 title claims abstract description 38
- 241001465754 Metazoa Species 0.000 title claims abstract description 31
- 230000001568 sexual effect Effects 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000001105 regulatory effect Effects 0.000 title claims description 13
- LYCYLGFSIXIXAB-NUZRHMIVSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(2s)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-h Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 LYCYLGFSIXIXAB-NUZRHMIVSA-N 0.000 title abstract 2
- 108700025485 deslorelin Proteins 0.000 title abstract 2
- 229960004165 deslorelin acetate Drugs 0.000 title abstract 2
- 238000002347 injection Methods 0.000 claims abstract description 41
- 239000007924 injection Substances 0.000 claims abstract description 41
- 239000007929 subcutaneous injection Substances 0.000 claims abstract description 14
- 238000010254 subcutaneous injection Methods 0.000 claims abstract description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 7
- 238000003860 storage Methods 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 4
- 238000009395 breeding Methods 0.000 abstract description 11
- 230000001488 breeding effect Effects 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 7
- 230000003203 everyday effect Effects 0.000 abstract description 3
- 230000001360 synchronised effect Effects 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 47
- 230000012173 estrus Effects 0.000 description 13
- 230000035935 pregnancy Effects 0.000 description 12
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 7
- 230000013011 mating Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 108700012941 GNRH1 Proteins 0.000 description 5
- NGCGMRBZPXEPOZ-HBBGHHHDSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)- Chemical compound CC(O)=O.C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 NGCGMRBZPXEPOZ-HBBGHHHDSA-N 0.000 description 5
- 229960005122 gonadorelin acetate Drugs 0.000 description 5
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 4
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 4
- 102000009151 Luteinizing Hormone Human genes 0.000 description 4
- 108010073521 Luteinizing Hormone Proteins 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229940028334 follicle stimulating hormone Drugs 0.000 description 4
- 229940040129 luteinizing hormone Drugs 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 2
- 210000003756 cervix mucus Anatomy 0.000 description 2
- 210000004246 corpus luteum Anatomy 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008227 sterile water for injection Substances 0.000 description 2
- 238000011121 vaginal smear Methods 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 101150108262 gnrh1 gene Proteins 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
-
- 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
Definitions
- the invention relates to the field of sexual cycle regulating drugs, and in particular to application of deserorelin acetate in preparing drugs for regulating the sexual cycle of animals.
- the prior art generally monitors the natural sexual cycle of female adult rats by sampling vaginal secretions.
- the vaginal secretions of the rats are taken, and the morphology of the vaginal cell fragments in the secretions is observed, and compared with the characteristics of the secretions of the rats during estrus, so as to determine whether the rats are currently in estrus. If they are in estrus, male rats are arranged for mating; if they are not in estrus, vaginal smears are continuously collected every day, waiting for the animals to enter estrus. Animals that are continuously not in estrus are eliminated.
- the present invention proposes the use of deserorelin acetate in the preparation of drugs for regulating the sexual cycle of animals.
- drugs are used to synchronize the animal cycle and improve the breeding efficiency for adult female rats with sexual cycle disorders.
- the invention provides application of deserorelin acetate in preparing a drug for regulating animal sexual cycle.
- the animal is a rat.
- the medicine is an injection.
- the dosage of deserorelin acetate is 20-40 ⁇ g/mouse.
- the administration dose of deserorelin acetate was 20 ⁇ g/mouse.
- the administration dose of deserorelin acetate was 40 ⁇ g/mouse.
- the drug is administered by injection, and the injection method is any one of subcutaneous injection or intradermal injection, preferably subcutaneous injection.
- the present invention also provides the use of deserorelin acetate as the only active ingredient in the preparation of a medicine for regulating the sexual cycle of animals.
- the present invention also provides a drug for regulating the sexual cycle of animals, wherein deserorelin acetate is the only active ingredient.
- the present invention also provides a method for preparing the drug, comprising the following steps: taking out the storage solution of deserorelin acetate, placing it on ice to completely dissolve it, and using a 1 ml syringe to draw the storage solution of deserorelin acetate for standby use.
- the use of the drug of the present invention does not require daily sampling of each animal, and does not require continuous monitoring of the animal's sexual cycle. Therefore, a large amount of time and labor costs can be saved in large-scale breeding needs.
- the sexual cycle of rats can be determined without relying on the staff's experience in identifying the sexual cycle of animals, thereby achieving the effect of accurate breeding.
- the estrus period of female adult rats can be accurately predicted and breeding can be precisely arranged.
- the conception date of female rats can be controlled, thus saving breeding time and improving breeding efficiency.
- accurate prediction of the estrus period in advance also reserves sufficient time for subsequent gene editing experiment preparations, which helps to improve work efficiency.
- the drug of the present invention is used to regulate the sexual cycle of female rats, and the pregnancy rate of female rats is as high as 100%.
- the administration route of the present invention is simple and easy to learn, and the operator can master it without a lot of practice.
- FIG. 1 is a schematic flow chart of an experimental method proposed in an embodiment of the present invention.
- Desserelin acetate is a structural analogue of LHRH (gonadotropin-releasing hormone) and has similar physiological effects to LHRH in the body.
- Gonadotropin-releasing hormone is a releasing hormone secreted by the hypothalamus, which acts on the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- FSH and LH act on the ovaries.
- the main function of FSH is to promote the development and maturation of follicles and the secretion of estrogen, while the main function of LH is to promote female ovulation and corpus luteum production, and to promote the secretion of estrogen and progesterone by the corpus luteum. Therefore, additional supplementation of LHRH structural analogues can adjust the sexual cycle of rats.
- the invention uses a method of subcutaneously injecting desserelin acetate into female adult rats through the neck skin to adjust the sexual cycle of female rats. After 72 hours of the injection, mating with male rats can successfully conceive.
- Drug Desorelin acetate/gonadorelin acetate.
- Dissolution method Dissolve in sterile water for injection, pay attention to aseptic operation.
- Test animals Female adult rats
- Injection dose 20 ⁇ g (0.05 ml)
- Test animals Female adult rats
- Injection dose 40 ⁇ g (0.1 ml)
- Test animals Female adult rats
- Injection dose 40 ⁇ g (0.1 ml)
- Test animals Female adult rats
- Injection method intraperitoneal injection
- Injection dose 40 ⁇ g (0.1 ml)
- Test animals Female adult rats
- Injection dose 40 ⁇ g (0.1 ml)
- Test animals Female adult rats
- Example 1 The results showed that one of the three rats in Example 1 became pregnant, with a pregnancy rate of 33.3%; all of the five rats in Example 2 became pregnant, with a pregnancy rate of 100%; one of the four rats in Example 3 became pregnant, with a pregnancy rate of 25%; none of the three rats injected intraperitoneally in Example 5 became pregnant, with a pregnancy rate of 0.
- Examples 2-4 injected the same dose of the drug, but the injection method was different.
- the results showed that subcutaneous injection was better than intradermal injection, and intraperitoneal injection had no effect.
- the injection method was the same, both were subcutaneous injections, but the drug dosage was different, indicating that 40 ⁇ g/rat was better than 20 ⁇ g/rat.
- the above results show that desserelin acetate, as a drug for regulating the sexual cycle of rats, can achieve a 100% pregnancy rate in rats by subcutaneous injection and a dose of 40 ⁇ g/rat.
- Example 2 The same volume of drug and solvent were injected subcutaneously, and the pregnancy rates of the control group (Comparative Example 1) and the experimental group (Example 2) were compared.
- the pregnancy rate of Example 2 was 100%, and all 5 rats were pregnant.
- the pregnancy rate of Comparative Example 1 was 0, which ruled out the influence of the experimental operation on the pregnancy rate of rats.
- deserorelin acetate As a small polypeptide molecule, deserorelin acetate is very easy to be degraded. If taken orally, it is decomposed into amino acids by digestive enzymes in the small intestine, loses its structural similarity with Gnrh, and thus loses its function. Injection can ensure that the molecular structure of the drug is not destroyed and maintains its activity; and for subcutaneous injection, this injection route does not release the drug into the blood in one go, so it has a certain sustained release effect, and the drug effect is most obvious. Therefore, deserorelin acetate of the present invention is preferably administered by subcutaneous injection as a drug for regulating sexual cycles. As a drug, it is not necessary to add excipients, pay attention to the dilution method and solvent, timely subpackage and strictly store at low temperature, and prohibit repeated freezing and thawing.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La présente invention concerne une utilisation de l'acétate de desloréline dans la préparation d'un médicament destiné à ajuster le cycle sexuel d'un animal. L'animal est un rat, et le médicament est une solution injectable, de préférence administrée par injection sous-cutanée. L'utilisation du médicament de la présente invention évite d'avoir à procéder à un prélèvement sur chaque animal tous les jours, ce qui permet des économies significatives en termes de temps et de coût de main-d'œuvre, et le cycle sexuel du rat peut être déterminé sans dépendre de l'expérience du personnel dans la détermination du cycle sexuel de l'animal, ce qui a pour effet d'entraîner une reproduction précise et, en ce qui concerne un trouble du cycle sexuel de la ratte adulte, le cycle de l'animal est synchronisé et l'efficacité de la reproduction est améliorée à l'aide du médicament, et le taux de conception de la ratte peut aller jusqu'à 100 %.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2022/126514 WO2024082230A1 (fr) | 2022-10-20 | 2022-10-20 | Utilisation d'acétate de desloréline dans la préparation d'un médicament destiné à réguler le cycle sexuel d'un animal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2022/126514 WO2024082230A1 (fr) | 2022-10-20 | 2022-10-20 | Utilisation d'acétate de desloréline dans la préparation d'un médicament destiné à réguler le cycle sexuel d'un animal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024082230A1 true WO2024082230A1 (fr) | 2024-04-25 |
Family
ID=90736554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2022/126514 WO2024082230A1 (fr) | 2022-10-20 | 2022-10-20 | Utilisation d'acétate de desloréline dans la préparation d'un médicament destiné à réguler le cycle sexuel d'un animal |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2024082230A1 (fr) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050130894A1 (en) * | 2003-10-03 | 2005-06-16 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| CN111202837A (zh) * | 2018-11-22 | 2020-05-29 | 中国农业大学 | 一种用于控制马属动物排卵的制剂及控制排卵的方法 |
| US20200376002A1 (en) * | 2019-05-30 | 2020-12-03 | Applied Technologies Consultants Inc. | Injectable Hormone Formulations for Estrous Cycle Control in Mammals, its Manufacturing Process, Estrous Cycle Control and Puberty Triggering Methods, and Pregnancy Enhancement in Mammals |
-
2022
- 2022-10-20 WO PCT/CN2022/126514 patent/WO2024082230A1/fr unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050130894A1 (en) * | 2003-10-03 | 2005-06-16 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| CN111202837A (zh) * | 2018-11-22 | 2020-05-29 | 中国农业大学 | 一种用于控制马属动物排卵的制剂及控制排卵的方法 |
| US20200376002A1 (en) * | 2019-05-30 | 2020-12-03 | Applied Technologies Consultants Inc. | Injectable Hormone Formulations for Estrous Cycle Control in Mammals, its Manufacturing Process, Estrous Cycle Control and Puberty Triggering Methods, and Pregnancy Enhancement in Mammals |
Non-Patent Citations (3)
| Title |
|---|
| CARLSON, D.A. ; GESE, E.M.: "Influence of exogenous gonadotropin-releasing hormone on seasonal reproductive behavior of the coyote (Canis latrans)", THERIOGENOLOGY, LOS ALTOS, CA, US, vol. 72, no. 6, 1 October 2009 (2009-10-01), US , pages 773 - 783, XP026521981, ISSN: 0093-691X, DOI: 10.1016/j.theriogenology.2009.05.012 * |
| CUIPING YU: "Factors Influencing Estrous Cycle of Female Canine and Estrus Induction", HEILONGJIANG JOURNAL OF ANIMAL REPRODUCTION, vol. 18, no. 5, 31 December 2010 (2010-12-31), pages 1 - 4, XP093162554, ISSN: 1005-2739 * |
| YAPAN SONG: "GnRH Analogs and Its Application on the Animal Reproduction", CHINA DAIRY CATTLE, no. 3, 31 December 2010 (2010-12-31), pages 22 - 26, XP093162571, ISSN: 1004-4264 * |
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