Application of DFO and composition thereof in functional recovery after ovarian transplantation
The combined application of DFO and VEGF-A has solved the problems of follicle loss and shortened functional recovery period after ovarian transplantation, achieving an increase in the number of follicles and the restoration of ovarian function and structure, and providing a safe and effective drug strategy.
Patent Information
- Application Number
- CN202511376099.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-25
- Publication Date
- 2025-12-12
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In existing technologies, the recovery period of ovarian function after cryopreservation-thaw transplantation of ovarian tissue is shortened, and follicle loss is severe. How to improve follicle survival rate and promote ovarian function recovery is a difficult problem in the field of fertility preservation.
The combined use of DFO and its pharmaceutically acceptable salts with VEGF-A or its pharmaceutically acceptable salts, administered locally or systemically, synergistically promotes the functional recovery of ovarian transplantation. The ratio of DFO to VEGF-A in the drug composition is 100:0.008, and simultaneous or sequential administration can be selected as needed.
It significantly improves follicle survival rate, increases follicle number, and restores ovarian function and structure. The combined use of DFO and VEGF-A has a synergistic effect, providing an effective drug strategy for functional recovery after ovarian transplantation.
Smart Images
Figure CN121102212A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of biological medicine, and in particular relates to application of DFO and a composition thereof in functional recovery after ovary transplantation. BACKGROUND
[0002] With the progress of diagnosis and treatment technology of malignant tumors, the survival rate of malignant tumor patients has been significantly improved. However, during the treatment of female malignant tumor patients by chemotherapy and radiotherapy, the gonadal ability is often damaged, resulting in decreased fertility. Clinicians and laboratory personnel can provide help to women at risk of infertility or men at risk of infertility by surgery, drugs or laboratory techniques to protect and preserve their ability to produce genetic offspring, that is, fertility preservation. For prepubertal women, women who need to immediately receive malignant tumor treatment and women with hormone-sensitive tumor (such as estrogen receptor-positive breast cancer) diseases, ovarian tissue cryopreservation is an effective choice for fertility preservation.
[0003] Ovarian tissue cryopreservation-recovery transplantation technology refers to that all or part of the ovary of a patient in need of fertility preservation is surgically removed, fragmented and then frozen, and then stored in liquid nitrogen or a mechanical freezer for long-term cryopreservation. After the disease is cured, the cryopreserved ovarian tissue is recovered and transplanted back into the body. Although most of the cases of ovarian tissue recovery and transplantation back into the pelvic cavity recover ovarian function, the post-transplantation ovarian function period is significantly shortened, and most of the follicles are lost during the ovarian tissue cryopreservation-recovery transplantation process. How to reduce follicle loss during treatment, improve the follicle survival rate of transplanted ovarian tissue and promote the functional recovery of transplanted ovarian tissue has become a technical problem to be solved in the field of fertility preservation. SUMMARY
[0004] As used herein, the terms "have", "comprise" or "include" or any grammatical variants thereof are used in a non-exclusive sense. Thus, these terms can mean that, in addition to the features introduced by these terms, the entity described in the context can also have other features, and can mean that in addition to the existence of one or more other features.
[0005] In addition, as used in the present application, the terms "preferably", "more preferably", "most preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in connection with optional features and do not restrict other possibilities.
[0006] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, percent, time, density, weight percent, technical effect, etc. in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations. Each numerical value should be considered in light of the number of significant figures used in that value and by the customary rounding off technique when approximating numerical values to the number of significant figures reported and by the typical measuring and handling techniques of one skilled in the art when approximating numerical values to the number of significant figures reported and by the typical measuring and handling techniques of one skilled in the art.
[0007] To make up for the deficiencies of the prior art, the present application provides the use of DFO and its composition in post-ovarian transplantation function recovery, and provides a safe and effective drug, a pharmaceutical composition, a pharmaceutical preparation, an intelligent diagnosis and treatment method, a system, equipment, a computer-readable storage medium or a computer program product, including a computer program, for post-ovarian transplantation function recovery.
[0008] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:
[0009] The present application provides a drug for promoting post-ovarian transplantation function recovery, and the drug is DFO or a pharmaceutically acceptable salt thereof.
[0010] Further, the individual mass of the DFO or the pharmaceutically acceptable salt thereof is 100 mg per kilogram.
[0011] In some embodiments, the pharmaceutically acceptable salt is safe and effective for local application in mammals and has the desired biological activity. The pharmaceutically acceptable salt includes a salt of an acidic or basic group present in the specified compound. The pharmaceutically acceptable acid addition salt includes, but is not limited to, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e. l, l'-methylene-bis-(2-hydroxy-3-naphthoate)). Some compounds used in the present application can form pharmaceutically acceptable salts with various amino acids. Suitable base salts include, but are not limited to: aluminum, calcium, lithium, magnesium, potassium, sodium, zinc and diethanolamine salts.
[0012] In some embodiments, the DFO corresponds to a hydrate, an enantiomer, a diastereomer, a solvate, a crystalline form or a derivative thereof, which are also within the protection scope of the present application, i.e. the use of the DFO corresponds to a hydrate, an enantiomer, a diastereomer, a solvate, a crystalline form or a derivative thereof in the preparation of a drug for promoting the functional recovery after ovary transplantation also falls within the protection scope of the present application.
[0013] The second aspect of the present application provides a pharmaceutical composition for promoting the functional recovery after ovary transplantation, wherein the active ingredients of the pharmaceutical composition are composed of DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof.
[0014] Further, the mass ratio of the DFO or a pharmaceutically acceptable salt thereof to the VEGF-A or a pharmaceutically acceptable salt thereof is 100:0.008.
[0015] Further, the individual mass of the DFO or a pharmaceutically acceptable salt thereof is 100 mg per kilogram.
[0016] Further, the individual mass of the VEGF-A or a pharmaceutically acceptable salt thereof is 8 μg per kilogram.
[0017] Further, the DFO or a pharmaceutically acceptable salt thereof in combination with the VEGF-A or a pharmaceutically acceptable salt thereof has a synergistic effect on the functional recovery after ovary transplantation.
[0018] In some embodiments, the DFO or a pharmaceutically acceptable salt thereof and the VEGF-A or a pharmaceutically acceptable salt thereof in the pharmaceutical composition can be administered simultaneously, separately or sequentially. Among them, simultaneously means that the two drugs are administered synchronously. If not administered simultaneously, they are administered sequentially within a time range, so that both can function therapeutically within the same time range. Therefore, sequential administration can allow the administration of one drug within 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours or several hours after the administration of the other drug, provided that the circulating half-life of the first administered drug allows both to exist simultaneously in a therapeutically effective amount. The time delay between the administration of each component will vary depending on the exact nature of the components, the interaction between them and their respective half-lives. Unlike simultaneously or sequentially, separately means that there is a significant interval between the administration of one drug and the other, i.e. when the second drug is administered, the first administered drug can no longer exist in a therapeutically effective amount in the bloodstream.
[0019] In some embodiments, the pharmaceutical compositions described herein can also be used in combination with other therapeutic compounds that are useful in the treatment and / or adjunct treatment of functional recovery after ovarian transplantation. The other therapeutic compounds can be administered simultaneously with, even in the same composition as, the primary active ingredient of the pharmaceutical compositions described herein. The other therapeutic compounds can also be administered separately from, but at a different dose from, the primary active ingredient. Part of the dose of the primary ingredient can be administered simultaneously with the other therapeutic compound, while other doses can be administered separately. The dose of the pharmaceutical compositions described herein can be adjusted during treatment according to the severity of the symptoms, the frequency of recurrence, and the physiological response to the treatment regimen.
[0020] In some embodiments, a therapeutically effective amount means that amount of an active compound or pharmaceutical agent that elicits the biological or medical response that is being sought in a tissue, system, animal, or human by a researcher, veterinarian, medical doctor or other clinician. The therapeutically or pharmaceutically effective amount of a compound to be administered will be governed by such considerations, and is the minimum amount necessary to ameliorate, cure, or treat a disease or condition or one or more symptoms thereof. The pharmaceutical compositions of the present application will be formulated, dosed, and administered in a fashion consistent with good medical practice, in accordance with the relevant field of use, and at dosages and
[0021] In some embodiments, the subject can be a human or non-human, and can include an animal strain or species used as a "model system" for research purposes, for example. Likewise, the subject can include an adult or a juvenile (e.g., a child). Further, the subject can refer to any living organism, preferably a mammal (e.g., a human or non-human). Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates (e.g., chimpanzees) and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; and laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. Examples of non-mammals include, but are not limited to, birds, fish, and the like.
[0022] The third aspect of the present application provides use of the DFO or a pharmaceutically acceptable salt thereof according to the first aspect of the present application or the DFO or a pharmaceutically acceptable salt thereof according to the second aspect of the present application in combination with VEGF-A or a pharmaceutically acceptable salt thereof in the preparation of a medicament for promoting functional recovery after ovarian transplantation.
[0023] The fourth aspect of the present application provides a pharmaceutical preparation for promoting functional recovery after ovary transplantation, wherein the pharmaceutical preparation comprises the drug of the first aspect of the present application or the pharmaceutical composition of the second aspect of the present application.
[0024] Further, the pharmaceutical preparation further comprises a pharmaceutically acceptable excipient.
[0025] In some embodiments, the pharmaceutically acceptable excipient of the present application comprises, but is not limited to, a diluent, a binder, a surface active agent, a wetting agent, an adsorption carrier, a lubricant, a filler, a disintegrant.
[0026] In specific embodiments, the diluent comprises, but is not limited to, lactose, sodium chloride, glucose, urea, starch, water, etc.
[0027] In specific embodiments, the binder comprises, but is not limited to, starch, pregelatinized starch, dextrin, maltodextrin, sucrose, gum arabic, gelatin, methyl cellulose, carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, polyethylene glycol, polyvinyl pyrrolidone, alginic acid and alginic acid salt, xanthan gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, etc.
[0028] In specific embodiments, the surface active agent comprises, but is not limited to, polyoxyethylene sorbitan fatty acid ester, sodium dodecyl sulfate, stearic acid monoglyceride, cetyl alcohol, etc.
[0029] In specific embodiments, the wetting agent comprises, but is not limited to, glycerol, starch, etc.
[0030] In specific embodiments, the adsorption carrier comprises, but is not limited to, starch, lactose, bentonite, silica gel, kaolin, soap clay, etc.
[0031] In specific embodiments, the lubricant comprises, but is not limited to, zinc stearate, glycerol monostearate, polyethylene glycol, talc, calcium and magnesium stearate, polyethylene glycol, boric acid powder, hydrogenated vegetable oil, sodium stearate fumarate, polyoxyethylene monostearate, monolauryl sucrose acid ester, sodium lauryl sulfate, magnesium lauryl sulfate, magnesium dodecyl sulfate, etc.
[0032] In specific embodiments, the filler comprises, but is not limited to, mannitol, xylitol, sorbitol, maltose, erythrose, microcrystalline cellulose, polymeric sugar, coupled sugar, glucose, lactose, sucrose, dextrin, starch, sodium alginate, kelp polysaccharide powder, agar powder, calcium carbonate, sodium bicarbonate, etc.
[0033] In specific embodiments, the disintegrant comprises, but is not limited to, cross-linked vinyl pyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl, cross-linked sodium carboxymethyl cellulose, soybean polysaccharide, etc.
[0034] In some embodiments, the pharmaceutical composition described in the present application can further comprise additives such as stabilizers, buffers, bactericides, isotonic agents, pH control agents, surfactants, and chelating agents.
[0035] Further, the dosage form of the pharmaceutical preparation includes an oral administration dosage form, a parenteral administration dosage form, or a topical administration dosage form.
[0036] In some embodiments, the dosage form of the pharmaceutical preparation described in the present application is not particularly limited, and is a dosage form that can be suitable for oral administration, parenteral administration, or topical administration, external administration, including but not limited to: injection solution, tablet, capsule, granule, powder, injection powder, transdermal patch, ointment, gel, suppository, oral solution, oral suspension, injection emulsion, oral emulsion, sustained-release tablet, controlled-release tablet. The pharmaceutical preparation of the various dosage forms described above can be prepared according to the conventional method in the pharmaceutical field.
[0037] The fifth aspect of the present application provides an intelligent diagnosis and treatment method for post-transplant ovarian function recovery based on DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof, which comprises the following steps:
[0038] S101: Obtain information related to post-transplant ovarian function elements of the subject.
[0039] S102: Determine whether the subject is a post-transplant ovarian function repair patient based on the information related to post-transplant ovarian function elements of the subject.
[0040] S103: When the subject is a post-transplant ovarian function repair patient, select the following treatment regimen: administer a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof to the subject.
[0041] Further, the post-transplant ovarian function element information includes surgical history, symptom manifestation, and / or examination data: laboratory examination data and / or pathological examination data.
[0042] Further, if the laboratory examination data in the examination data shows that the number of follicles, follicle survival rate, primary follicle ratio, and / or antral follicle ratio of the subject are lower than the normal range, the atretic follicle ratio is higher than the normal range, and / or the pathological examination data shows that the ovarian tissue structure is damaged, the subject is matched as a post-transplant ovarian function repair patient.
[0043] If the laboratory examination data in the examination data shows that the number of follicles, follicle survival rate, primary follicle ratio, antral follicle ratio, and / or atretic follicle ratio of the subject are within the normal range and / or the pathological examination data shows that the ovarian tissue structure is intact, the subject is matched as a non-post-transplant ovarian function repair patient.
[0044] The sixth aspect of the present application provides an intelligent diagnosis and treatment system for post-ovarian transplantation function recovery based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof, the system comprising:
[0045] a diagnosis element information collector for collecting the post-ovarian transplantation function element information according to the fifth aspect of the present application and sending the collected data results to a disease diagnosis matcher.
[0046] a disease diagnosis matcher for matching the post-ovarian transplantation function element information collected by the diagnosis element information collector with disease types and sending the matched data results to a treatment scheme matcher.
[0047] a treatment scheme matcher for determining the results matched by the disease diagnosis matcher and calling a treatment scheme according to the matched results, and sending the treatment scheme data results to a disease diagnosis and treatment information outputter.
[0048] a disease diagnosis and treatment information outputter for outputting the data results received from the disease diagnosis matcher and the treatment scheme matcher to a receiving unit.
[0049] In the treatment scheme matcher, if the disease diagnosis matcher matches the subject as a post-ovarian transplantation function repair patient, the following treatment scheme is matched and called: administering a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof to the subject.
[0050] In the treatment scheme matcher, if the disease diagnosis matcher matches the subject as a non-post-ovarian transplantation function repair patient, the following treatment scheme does not need to be matched and called: administering a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof to the subject.
[0051] Further, the receiving unit is a display screen, a computer client, a mobile phone client or a tablet computer.
[0052] The seventh aspect of the present application provides an intelligent diagnosis and treatment computer device, a computer readable storage medium or a computer program product based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof for post-ovarian transplantation function recovery, comprising a computer program, the device comprising a memory and a processor, the memory being used for storing program instructions; the processor is used for calling program instructions, when the program instructions are executed, the steps of the intelligent diagnosis and treatment method for post-ovarian transplantation function recovery based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof according to the fifth aspect of the present application are realized.
[0053] The computer readable storage medium stores a computer program, and the computer program is executed by a processor to implement the steps of the intelligent diagnosis and treatment method for recovery of ovarian function after transplantation based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof according to the fifth aspect of the present application.
[0054] The computer program is executed by a processor to implement the steps of the intelligent diagnosis and treatment method for recovery of ovarian function after transplantation based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof according to the fifth aspect of the present application.
[0055] Advantages and beneficial effects of the present application:
[0056] The present application first discovers that DFO can effectively improve the follicle survival rate, increase the number of follicles, and restore the functional structure of the ovary. At the same time, the present application first discovers that DFO and VEGF-A have a synergistic effect on the recovery of ovarian function after transplantation. The present application provides an effective drug and drug combination strategy for the recovery of ovarian function after transplantation, and has a wide application prospect in the technical field of development of drugs for repairing the ovary after transplantation. BRIEF DESCRIPTION OF DRAWINGS
[0057] Figure 1 A flowchart of an intelligent diagnosis and treatment method for recovery of ovarian function after transplantation based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof is provided for an embodiment of the present application.
[0058] Figure 2 A structure diagram of an intelligent diagnosis and treatment system for recovery of ovarian function after transplantation based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof is provided for an embodiment of the present application.
[0059] Figure 3 A computer device diagram of an intelligent diagnosis and treatment system for recovery of ovarian function after transplantation based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof is provided for an embodiment of the present application.
[0060] Figure 4 Effects of DFO and DFO in combination with VEGF-A on follicle morphology after ovary transplantation. DETAILED DESCRIPTION
[0061] The application will be further described in conjunction with specific examples. The following specific examples are only used to explain the application and cannot be understood as a limitation of the application. Those skilled in the art can understand that various changes, modifications, replacements and variations can be made to the examples without departing from the principles and purposes of the application, and the scope of the application is defined by the claims and their equivalents. The experimental consumables, reagents and raw materials used in the application are easily obtained by those skilled in the art, and if not specifically stated, they can be obtained from commercial channels. The experimental methods of the application not specified in the application are usually carried out according to the conventional conditions or the conditions recommended by the manufacturer. In particular, the following examples are only used to illustrate the application and should not limit the scope of the application in any way. It should be noted that the experimental conditions and results described in the following examples are only used to illustrate the application and should not and will not limit the application described in detail in the claims.
[0062] In order for those skilled in the art to better understand the solutions of the present application, the technical solutions in the embodiments of the present application will be described clearly and completely in conjunction with the drawings in the embodiments of the present application. In some processes described in the specification and claims of the present application and the above-mentioned drawings, a plurality of operations appearing in a specific order are included, but it should be clearly understood that these operations can be executed or performed in parallel without the order appearing in this text. The serial numbers of the operations such as S101, S102, S103, etc. are only used to distinguish different operations, and the serial numbers themselves do not represent any execution order. In addition, these processes can include more or fewer operations, and the operations can be executed in sequence or in parallel.
[0063] The technical solutions in the embodiments of the present application will be described clearly and completely in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the protection scope of the present application.
[0064] Figure 1 is a smart diagnosis and treatment method flowchart for functional recovery after ovary transplantation provided by an embodiment of the present application based on DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof. Specifically, the method comprises:
[0065] S101: obtaining subject-related post-ovary transplantation function element information.
[0066] S102: determining whether the subject is a post-ovary transplantation function repair patient based on the subject-related post-ovary transplantation function element information data.
[0067] S103: when the subject is a patient whose post-ovarian transplantation function needs to be repaired, a treatment regimen is selected: administering to the subject a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof.
[0068] In some embodiments, the post-ovarian transplantation function element information includes surgical history, symptom manifestation, and / or examination data: laboratory examination data and / or pathological examination data.
[0069] In some embodiments, if the laboratory examination data in the examination data shows that the subject's follicle number, follicle survival rate, primary follicle ratio, and / or antral follicle ratio value is lower than the normal range, the atretic follicle ratio value is higher than the normal range, and / or the pathological examination data shows that the ovarian tissue structure is damaged, the subject is matched as a patient whose post-ovarian transplantation function needs to be repaired.
[0070] If the laboratory examination data in the examination data shows that the subject's follicle number, follicle survival rate, primary follicle ratio, antral follicle ratio, and / or atretic follicle ratio value is within the normal range and / or the pathological examination data shows that the ovarian tissue structure is intact, the subject is matched as a patient whose post-ovarian transplantation function does not need to be repaired.
[0071] In some embodiments, the post-ovarian transplantation function element information is not limited to the above-mentioned surgical history, symptom manifestation, and / or examination data. Any information known to those skilled in the art that can be used to determine the post-ovarian transplantation function element is included in the post-ovarian transplantation function element information of the present application. In addition, those skilled in the art can determine whether the subject is a patient whose post-ovarian transplantation function needs to be repaired based on the above-mentioned post-ovarian transplantation function element information and the diagnostic criteria known in the art.
[0072] It should be noted that the innovation of the present application is not in the method of determining the post-ovarian transplantation function, but in the treatment regimen for the patient whose post-ovarian transplantation function needs to be repaired: administering to the subject (i.e., the patient whose post-ovarian transplantation function needs to be repaired) a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof.
[0073] In a specific embodiment, the present application proves that DFO and DFO in combination with VEGF-A can significantly improve the follicle survival rate of post-ovarian transplantation mice and restore ovarian function, and DFO in combination with VEGF-A has a synergistic effect, which suggests the feasibility of the intelligent diagnosis and treatment method for post-ovarian transplantation function recovery based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof. Specifically as follows:
[0074] I. Experimental methods
[0075] 1. Experimental materials:
[0076] (1) Experimental animals: C57 mice, female, 12-16 weeks old, 8 in each group.
[0077] (2) Drugs:
[0078] DFO, MCE company, 434644;
[0079] VEGF-A, MCE company, HY-J19145;
[0080] Pregnant mare serum gonadotropin (PMSG), Solaybao, 2503190001;
[0081] Human chorionic gonadotropin (hCG), Shanghai Maikelin, C17119846.
[0082] (3) Experimental grouping:
[0083] ① Normal group: normal saline;
[0084] ② OTT (ovarian tissue transplantation) group: ovarian tissue transplantation;
[0085] ③ DFO+OTT group: after ovarian transplantation, DFO 100 mg / kg / d, intraperitoneal injection for 21 days;
[0086] ④ VEGF-A+OTT group: after ovarian transplantation, VEGF-A 8 μg / kg / d, intraperitoneal injection for 1-5 days after operation;
[0087] ⑤ DFO+VEGF-A+OTT group: after ovarian transplantation, DFO 100 mg / kg / d, intraperitoneal injection for 21 days; combined with VEGF-A 8 μg / kg / d, intraperitoneal injection for 1-5 days after operation.
[0088] 2. Experimental steps
[0089] (1) OTT model: each mouse was intraperitoneally injected with 0.1 ml of 1.5% sodium pentobarbital anesthesia, the back was prepared for skin, a small incision was made at the inguinal region 2 cm above, the fat was clamped with forceps, the ovarian tissue was taken out, the connection between the ovary and the fallopian tube was cut off, and the fine forceps were used to clamp the ovary and the fat between them. The ovary was taken out and temporarily placed in a culture dish containing normal saline. The same incision exposed the kidney, a small incision was made on the kidney capsule with a sterile blade, the capsule was gently lifted with a fine forceps, and the ipsilateral ovary was placed into the kidney. The kidney was reduced and the incision was sutured. After the transplantation was completed, 0.2 ml of normal saline was injected every day, and after 21 days, ovulation was induced, the ovarian tissue was taken out, and the follow-up detection was carried out.
[0090] (2) Detection of follicle number: 21 days after ovary transplantation, mice were injected intraperitoneally with 10 IU of PMSG (100 IU / ml, 100 μl / each), and 48 hours later, an equivalent dose of hCG (100 IU / ml, 100 μl / each) was administered to promote ovulation. The ovaries were removed 16 hours after hCG administration, fixed with 4% paraformaldehyde, and subjected to HE staining.
[0091] II. Experimental results
[0092] (1) Effect of DFO and DFO combined with VEGF-A on follicle number after ovary transplantation
[0093] Compared with the Con group, the OTT group had a reduced follicle number and survival rate; the DFO+OTT group significantly increased the follicle number and survival rate after ovary transplantation, and the DFO+VEGF-A+OTT group had a synergistic effect on the increase in follicle number and follicle survival rate (Table 1).
[0094] Table 1. Follicle number and follicle survival rate (n=7)
[0095]
[0096] # P<0.05 vs OTT
[0097] (2) Effect of DFO and DFO combined with VEGF-A on the ratio of follicles at different stages after ovary transplantation
[0098] Compared with the Con group, the OTT group had a reduced ratio of primary follicles and antral follicles and an increased ratio of atretic follicles; the DFO+OTT group and the DFO+VEGF-A+OTT group both significantly reversed this change, and the DFO+VEGF-A+OTT group had a synergistic effect (Table 2).
[0099] Table 2. Ratio of follicles at different stages to total follicles (%)
[0100]
[0101] # P<0.05 vs OTT
[0102] (3) Effect of DFO and DFO combined with VEGF-A on follicle morphology after ovary transplantation
[0103] The overall structure of the ovary tissue of the mice in the Con group was complete, and the ovary granulosa cells were rich and closely arranged; compared with the control group, the overall structure of the ovary tissue of the mice in the OTT group was damaged, the cells were scattered and disordered, the ovary granulosa cells were loosely arranged and disordered, and the atretic follicles increased; compared with the OTT group, the overall structure of the ovary tissue of the mice in the DFO+OTT group and the DFO+VEGF-A+OTT group was improved, the atretic follicles decreased, and the DFO+VEGF-A+OTT group had a synergistic effect Figure 4 ).
[0104] Figure 2 is a schematic diagram of an intelligent diagnosis and treatment system for post-ovarian transplantation function recovery based on DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof provided by an embodiment of the present application. Specifically, the system comprises:
[0105] A diagnosis element information collector is configured to collect the post-ovarian transplantation function element information according to the fifth aspect of the present application and send the collected data results to a disease diagnosis matcher.
[0106] A disease diagnosis matcher is configured to match the function element information of the diagnosis element information collector with disease categories and send the matched data results to a treatment scheme matcher.
[0107] A treatment scheme matcher is configured to determine the matched results of the disease diagnosis matcher, match and call a treatment scheme according to the results, and send the treatment scheme data results to a disease diagnosis and treatment information outputter.
[0108] A disease diagnosis and treatment information outputter is configured to output the data results received by the disease diagnosis matcher and the treatment scheme matcher to a receiving unit.
[0109] In the treatment scheme matcher, if the disease diagnosis matcher matches the subject as a post-ovarian transplantation function repair patient, the following treatment scheme is matched and called: a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof is administered to the subject.
[0110] In the treatment scheme matcher, if the disease diagnosis matcher matches the subject as a non-post-ovarian transplantation function repair patient, the following treatment scheme does not need to be matched and called: a therapeutically effective amount of DFO or a pharmaceutically acceptable salt thereof combined with VEGF-A or a pharmaceutically acceptable salt thereof is administered to the subject.
[0111] In some embodiments, the receiving unit is a display screen, a computer client, a mobile phone client, or a tablet computer.
[0112] Figure 3The application provides an intelligent diagnosis and treatment computer device based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof for post-ovarian transplantation function recovery, and the device comprises a memory and a processor, the memory is used for storing program instructions, and the processor is used for calling the program instructions.
[0113] In some embodiments, the intelligent diagnosis and treatment computer device based on DFO or a pharmaceutically acceptable salt thereof in combination with VEGF-A or a pharmaceutically acceptable salt thereof for post-ovarian transplantation function recovery can further comprise an input device and an output device.
[0114] In some embodiments, the memory, the processor, the input device and the output device can be connected through a bus or other means. Figure 3 The above is an example of a bus connection mode; the memory is used for storing program instructions; the processor is used for calling the program instructions, and when the program instructions are executed, the above method is implemented.
[0115] In some embodiments, the memory can be understood as any storage device of a program, and the processor can be understood as a use device of the program.
[0116] In several embodiments provided in the present application, it should be understood that the disclosed system, device and method can be implemented in other ways. For example, the device embodiments described above are only schematic; for example, the division of the units is only a logical function division, and actual implementation can have another division manner, for example, a plurality of units or components can be combined or integrated into another system, or some features can be ignored or not executed. In addition, the coupling or direct coupling or communication connection between the units shown or discussed can be indirect coupling or communication connection through some interfaces, devices or units, and can be electrical, mechanical or other forms.
[0117] The units described as separate components can or can not be physically separated, and the components shown as units can or can not be physical units, that is, they can be located in one place, or can be distributed on a plurality of network units. According to actual needs, some or all of the units can be selected to achieve the purpose of the embodiment scheme.
[0118] In addition, each functional unit in each embodiment of the present application can be integrated in one processing unit, or each unit can exist physically, or two or more units can be integrated in one unit. The integrated unit can be realized in the form of hardware or in the form of a software functional unit.
[0119] Those skilled in the art can understand that all or part of the steps in the above-mentioned various methods of the embodiments can be completed by instructing the relevant hardware through a program, and the program can be stored in a computer readable storage medium, which can include a read only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk, etc.
[0120] The above describes in detail the computer device provided by the present application. For those skilled in the art, the specific implementation and application range can be changed according to the idea of the embodiments of the present application. In summary, the content of the specification should not be understood as a limitation of the present application.
[0121] The above description of the embodiments is only for understanding the method of the present application and its core idea. It should be pointed out that, for those skilled in the art, without departing from the principles of the present application, the present application can be improved and modified in several ways, and these improvements and modifications will also fall within the protection scope of the claims of the present application.
Claims
1. A drug for promoting functional recovery after ovarian transplantation, characterized in that, The drug is DFO or its pharmaceutically acceptable salt.
2. The drug according to claim 1, characterized in that, The DFO or its pharmaceutically usable salt contains 100 mg per kilogram.
3. A pharmaceutical composition for promoting functional recovery after ovarian transplantation, characterized in that, The active ingredient of the pharmaceutical composition is composed of DFO or its pharmaceutically acceptable salt in combination with VEGF-A or its pharmaceutically acceptable salt; Preferably, the mass ratio of DFO or its pharmaceutically acceptable salt to VEGF-A or its pharmaceutically acceptable salt is 100:0.008; Preferably, the DFO or its pharmaceutically acceptable salt per kilogram has an individual mass of 100 mg; Preferably, the individual mass of VEGF-A or its pharmaceutically usable salt is 8 μg per kilogram.
4. The use of the DFO of claim 1 or its pharmaceutically acceptable salt, or the DFO of claim 3 or its pharmaceutically acceptable salt in combination with VEGF-A or its pharmaceutically acceptable salt, in the preparation of a medicament for promoting ovarian function recovery after transplantation.
5. A pharmaceutical preparation for promoting functional recovery after ovarian transplantation, characterized in that, The pharmaceutical preparation comprises the drug of claim 1 or the pharmaceutical composition of claim 3; Preferably, the pharmaceutical preparation further includes pharmaceutically acceptable excipients; Preferably, the dosage form of the pharmaceutical preparation includes an oral dosage form, a parenteral dosage form, or a topical dosage form.
6. A smart diagnostic and treatment method for post-ovarian transplant functional recovery based on DFO or its pharmaceutically acceptable salts combined with VEGF-A or its pharmaceutically acceptable salts, characterized in that, The method includes the following steps: S101: Obtain relevant post-ovarian transplant functional information of the subject; S102: Determine whether the subject is a patient whose ovarian function needs to be repaired after ovarian transplantation based on the subject's relevant post-transplantation functional element information data; S103: When the subject is a patient whose ovarian function needs to be repaired after ovarian transplantation, the following treatment regimen shall be selected: administer a therapeutically effective amount of DFO or its pharmaceutically acceptable salt in combination with VEGF-A or its pharmaceutically acceptable salt to the subject.
7. The intelligent diagnostic and treatment method for post-ovarian transplant functional recovery based on DFO or its pharmaceutically acceptable salts combined with VEGF-A or its pharmaceutically acceptable salts, as described in claim 6, is characterized in that... The functional information after ovarian transplantation includes surgical history, symptoms and / or examination data: laboratory test data and / or pathological examination data; If the laboratory test data shows that the subject's follicle count, follicle survival rate, primordial follicle ratio and / or antral follicle ratio are below the normal range, the atretic follicle ratio is above the normal range, and / or the pathological examination data shows ovarian tissue structure damage, then the subject will be matched as a patient whose ovarian function needs to be repaired after ovarian transplantation. If the laboratory test data shows that the subject's follicle count, follicle survival rate, primordial follicle ratio, antral follicle ratio, and / or atretic follicle ratio are within the normal range and / or the pathological examination data shows that the ovarian tissue structure is intact, then the subject will be matched as a non-ovarian transplant recipient with functional repair needs.
8. A smart diagnostic and treatment system for post-ovarian transplant functional recovery based on DFO or its pharmaceutically acceptable salts combined with VEGF-A or its pharmaceutically acceptable salts, characterized in that, The system includes: A diagnostic element information collector is used to collect functional element information after ovarian transplantation as described in claim 7 and send the collected data results to a disease diagnosis matcher. The disease diagnosis matcher is used to match the functional element information of the diagnostic element information collector with the disease type, and send the matched data results to the treatment plan matcher. The treatment plan matcher is used to determine the matching result of the disease diagnosis matcher and call the treatment plan according to the result, and then send the treatment plan data result to the disease diagnosis and treatment information output device. The disease diagnosis and treatment information output device is used to output the data results received from the disease diagnosis matcher and treatment plan matcher to the receiving unit; In the treatment plan matcher, if the disease diagnosis matcher matches the subject as a patient whose ovarian function needs to be repaired after ovarian transplantation, the following treatment plan is matched and invoked: administer a therapeutically effective amount of DFO or its pharmaceutically acceptable salt in combination with VEGF-A or its pharmaceutically acceptable salt to the subject; In the treatment matching device, if the disease diagnosis matching device matches the subject as a non-ovarian transplant patient requiring functional repair, then there is no need to match and invoke the following treatment plan: administering a therapeutically effective amount of DFO or its pharmaceutically acceptable salt in combination with VEGF-A or its pharmaceutically acceptable salt to the subject.
9. The intelligent diagnostic and treatment system for post-ovarian transplant functional recovery based on DFO or its pharmaceutically acceptable salts combined with VEGF-A or its pharmaceutically acceptable salts, as described in claim 8, is characterized in that... The receiving unit can be a display screen, a computer client, a mobile client, or a tablet.
10. A computer device, computationally readable storage medium, or computer program product for intelligent diagnosis and treatment of post-ovarian transplantation functional recovery based on DFO or its pharmaceutically acceptable salts in combination with VEGF-A or its pharmaceutically acceptable salts, comprising a computer program, characterized in that, The device includes a memory and a processor. The memory is used to store program instructions. The processor is used to call the program instructions, and when the program instructions are executed, to implement the steps of the intelligent diagnostic and treatment method for post-ovarian transplantation function recovery based on DFO or its medicated salts combined with VEGF-A or its medicated salts as described in claim 6. The computer-readable storage medium stores a computer program, which, when executed by a processor, implements the steps of the intelligent diagnostic and treatment method for post-ovarian transplantation function recovery based on DFO or its medicated salts in combination with VEGF-A or its medicated salts as described in claim 6. When the computer program is executed by the processor, it implements the steps of the intelligent diagnostic and treatment method for ovarian function recovery after transplantation based on DFO or its medicinal salts in combination with VEGF-A or its medicinal salts as described in claim 6.