本文選題：卵泡刺激素 + 透明質(zhì)酸　； 參考：《華僑大學(xué)》2017年碩士論文

【摘要】：對于輔助生殖技術(shù)(Assisted reproductive technology,ART),如體外受精(In vitro fertilization,IVF)和胞漿內(nèi)精子注射(Intracytoplasmic sperminjection,ICSI),卵泡刺激激素(Folliclestimulating Hormone,FSH)的注射是實現(xiàn)超數(shù)排卵的必要步驟。目前臨床上常用的FSH制劑,存在半衰期短、需多次注射、患者依從性差等局限性,因此,FSH緩釋制劑的研究意義重大。緩釋制劑因其使用便利,療效佳,患者依從性好,安全性高而被人們廣泛接受,其中基于生物降解和生物溶蝕系統(tǒng)的FSH緩釋制劑是新型FSH制劑的主要研究方向。目前國內(nèi)外新型FSH制劑的研究主要集中在基于重組基因技術(shù)生產(chǎn)長效FSH的制劑,忽略了基于高分子化學(xué)等理論進(jìn)行FSH緩釋制劑的研制。其實,FSH緩釋制劑的研究前景也十分廣闊,其理論和應(yīng)用研究在不孕不育的臨床治療和畜牧業(yè)的發(fā)展方面意義深遠(yuǎn)!透明質(zhì)酸(Hyaluronan,HA)的衍生物透明質(zhì)酸鈉已成為臨床上常用的藥物緩釋載體。本實驗首先以透明質(zhì)酸鈉為輔料,將FSH荷載于透明質(zhì)酸凝膠,得到FSH緩釋制劑。并且基于卵巢增重法進(jìn)行了FSH緩釋凝膠的體內(nèi)生物活性檢測,并對透明質(zhì)酸鈉的使用濃度進(jìn)行初步篩選;隨后研究了FSH緩釋凝膠對卵巢增重大鼠的卵巢和子宮發(fā)育的影響;然后基于超數(shù)排卵用昆明小鼠進(jìn)行了藥效學(xué)研究。最后,為探究未成熟卵巢增重小鼠的卵巢發(fā)育機(jī)制及超數(shù)排卵對于小鼠卵巢發(fā)育、卵泡成熟的影響,本實驗還研究了卵巢發(fā)育過程中相關(guān)生長因子(表皮生長因子和胰島素樣生長因子I)和促性腺激素(卵泡刺激素和促黃體生成素)的受體的表達(dá)變化,以探究FSH緩釋凝膠對于卵巢和卵泡發(fā)育成熟的作用機(jī)制。上述研究表明,以透明質(zhì)酸為基質(zhì)制備得到的FSH緩釋凝膠,體內(nèi)生物活性高,單次注射即可達(dá)到市售FSH三次注射的卵巢增重效果。且其超數(shù)排卵效果顯著優(yōu)于市售超排藥物的作用和自然排卵。實驗證明HA濃度為5mg/mL,FSH劑量為5IU的FSH緩釋凝膠對于昆明小鼠的超數(shù)排卵效果為最佳。相關(guān)機(jī)制的研究,為闡明FSH的作用機(jī)理,及其藥理作用和醫(yī)藥研究奠定了基礎(chǔ)。綜上所述,本研究為制備成本低,藥效好,低副作用的FSH緩釋制劑提供了新的思路。
[Abstract]:The injection of assisted reproductive technology, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), Follicl estimation of Hormoneated FSHs, is a necessary step for the realization of superovulation. At present, the commonly used FSH preparations have some limitations, such as short half-life, multiple injections, poor compliance of patients and so on, so the study of FSH sustained-release preparations is of great significance. Sustained-release preparations are widely accepted for their convenience, efficacy, compliance and safety. Among them, FSH sustained-release preparation based on biodegradation and biodissolution system is the main research direction of new FSH preparations. At present, the research of new FSH preparations at home and abroad is mainly focused on the production of long-acting FSH based on recombinant gene technology, ignoring the development of FSH sustained-release preparations based on the theory of macromolecule chemistry. In fact, the research prospect of FSH sustained-release preparation is also very broad, its theory and application research in the clinical treatment of infertility and the development of animal husbandry far-reaching significance! Sodium hyaluronate, a derivative of Hyaluronan HA, has become a commonly used drug delivery carrier. In this experiment, sodium hyaluronate was used as excipient and FSH was loaded on hyaluronic acid gel to obtain FSH sustained-release preparation. The biological activity of FSH sustained-release gel was determined based on the method of ovarian weight gain, and the concentration of sodium hyaluronate was preliminarily screened, and the effects of FSH sustained-release gel on ovary and uterus development of ovarian weight increasing rats were studied. Then the pharmacodynamics of Kunming mice was studied based on superovulation. Finally, in order to explore the mechanism of ovarian development and the effect of superovulation on ovarian development and follicular maturation in immature ovarian weight gain mice, In this study, we also studied the changes of receptor expression of related growth factors (epidermal growth factor and insulin-like growth factor I) and gonadotropin (follicle stimulating hormone and luteinizing hormone) during ovarian development. To explore the mechanism of FSH sustained-release gel on ovarian and follicular development and maturation. The results showed that the FSH sustained-release gel prepared from hyaluronic acid had high bioactivity in vivo and could gain ovarian weight with three injections of FSH on the market. The effect of superovulation was better than that of superovulation drugs and natural ovulation. The results showed that FSH sustained-release gel with a concentration of 5 mg / mL FSH of 5IU had the best effect on the superovulation of Kunming mice. The study of the related mechanism laid a foundation for elucidating the action mechanism, pharmacological action and pharmaceutical research of FSH. In conclusion, this study provides a new idea for the preparation of FSH sustained-release preparations with low cost, good efficacy and low side effects.
【學(xué)位授予單位】：華僑大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943;R965

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