KR20010085046A - Effects of high molecular weight water-soluble chitosan on ovarian reaction and pregnancy in obesity mice. - Google Patents
Effects of high molecular weight water-soluble chitosan on ovarian reaction and pregnancy in obesity mice. Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/332—Promoters of weight control and weight loss
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/50—Polysaccharides, gums
- A23V2250/51—Polysaccharide
- A23V2250/511—Chitin, chitosan
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Abstract
Description
본 발명은 비만으로 인한 여성의 불임치료에서 수용성 키토산의 효과여부를 알아보기 위해 생쥐모델을 적용시킨 결과이다. 더욱 구체적으로, 본 발명은 비만생쥐와 정상생쥐에 키토산을 구강투여(Oral Administration)하여 체중감량에 따른 불임치료효과를 실험 한 결과 비만생쥐에 키토산을 일정량 먹인 집단이 그렇지 않은 집단보다 체지방 감소효과가 나타난다는 것을 알았다.The present invention is the result of applying a mouse model to determine the effect of water-soluble chitosan in infertility treatment of women due to obesity. More specifically, according to the present invention, an oral administration of chitosan to obese mice and normal mice (Oral Administration) resulted in the treatment of infertility according to weight loss. I knew it appeared.
수용성 키토산은 섭취하는 지방을 필요량 외에는 효과적으로 체외로 배출시킬 뿐 아니라, 체내에 축적되어 있던 과잉의 지방질도 서서히 분해하여 체외로 배출시키는 효과가 있다는 기존의 연구결과를 토대로 하여 본 연구에서는 비만인의 체중감소효과와 더불어 난소 주위의 지방질도 효과적으로 분해해 난소 비대의 감소와 난소기능 회복, 즉 비만으로 인한 월경 불순 및 배란장애의 예방 및 치료에 있어서 그 효과가 있다는 사실을 밝혀내었다.Water-soluble chitosan not only effectively drains fats from the body, but also dissolves excess fat that has accumulated in the body and releases it out of the body. In addition to the effects, the lipids around the ovary were effectively decomposed to reduce the ovarian hypertrophy and ovarian function, that is, it was found to be effective in the prevention and treatment of dysmenorrhea and ovulation disorders caused by obesity.
비만(Obesity)이란 대사장애로 인해 체내에 지방이 과잉 축적된 상태로 칼로리 섭취가 신체 활동과 성장에 필요한 에너지보다 초과되어 열량 불균형으로 일어나는 현상으로 남자는 체내의 지방이 체중의 25%이상, 여자는 체중의 30%이상인 경우를 말한다.Obesity is a phenomenon in which calorie inequality occurs due to excessive accumulation of fat in the body due to metabolic disorders, resulting in calorie imbalance due to excess energy required for physical activity and growth. Refers to the case of more than 30% of body weight.
비만의 원인은 유전적 요인, 식사습관, 심리적 장애, 중추신경계 이상, 호르몬 원인, 운동부족 등이 있으며 그 원인에 따라 단순성 비만과 중추성 비만, 성인에 따라 조절성 비만, 대사성 비만, 지방세포의 양에 따라 비대형, 증식형과 혼합형, 축적된 부위에 따라 중심성과 말초성 등으로 분류할 수 있다. 최근 우리나라는 경제적 발전과 서양문물의 영향으로 식생활 습관의 변화와 운동량의 부족, 스트레스 등으로 비만증의 발생이 증가하는 추세에 있다. 한편 불임의 원인에는 여성의 경우에 배란과 월경의 장애, 난관폐쇄나 자궁의 구조적 이상 등의 생식기 이상, 자궁내막증 및 염증성 질환의 생식기 질환, 면역학적요인 등이 있는데 그 중 비만으로 인한 배란장애가 높은 비율을 차지하고 있다. 부인과적으로 비만여성은 대부분 혈중성선자극호르몬(gonadotrophin)의 농도가 높고 남성호르몬인 Androgen이 높아, 난소(ovary)가 비대해지고 난소표면에 적은 난포(follicle)가 존재하는 것으로 알려져 있다. 이로 인해 비만여성에서는 핍배란(rare ovulation), 무월경(non-menstruation), 기능부전성자궁출현(malfunctioned vaginal hemorrhage) 등을 일으키는 난소기능의 이상이 나타날 수 있으며, 난소기능의 미세한 변화에 의해서 불임을 초래하기도 한다. 부인과적으로 비만여성은 대부분 혈중성선자극호르몬(gonadotrophin)의 농도가 높아 Androgen이 높고, 난소(ovary)비대와 난소표면의 적은 난포(follicle)가 존재하는 것으로 알려져 있다. 비만여성에게 저칼로리(low calorie) 식사와 체중감량을 시행하여 비만이 월경에 미치는 영향을 관찰한 바, 체중감소가 나타난 군에서는 월경주기가 정상적으로 회복되어 임신이 가능하였으나, 체중감량에 실패한 비만여성에서는 월경이 정상적으로 회복되지 못하였다. 또한 Androgen 과잉증, 무배란(anovulation) 소견을 보여 다낭성 난소증후군(polycystic ovary syndrome)으로 진단된 비만여성에서 체중감량으로 불임을 성공적으로 치료된 바가 있으며, 칼로리 제한과 체중감소를 통해 증가되었던 혈청 Androstenedione과 Testosterone 수치가 정상으로 회복되었다. 또한 체중이 과다하면 수정란의 착상이 실패할 수 있어 자궁내막에 문제가 생길 가능성이 높다. 따라서 비만여성에서 체중감량으로 성호르몬의 역동이 변화함에 따라 발생한 생식기능의 이상이 교정되므로 체중감량이 효과적인 치료 방법임을 알 수 있다.The causes of obesity are genetic factors, dietary habits, psychological disorders, central nervous system abnormalities, hormonal causes, and lack of exercise, depending on the causes of simple obesity, central obesity, controlled obesity, metabolic obesity, fat cells Depending on the amount, it can be classified into hypertrophic, proliferative and mixed, and accumulated and central. Recently, the development of obesity has been increasing in Korea due to changes in dietary habits, lack of exercise, and stress due to economic development and Western culture. The causes of infertility include female ovulation and menstrual disorders, genital abnormalities such as tubal obstruction or structural abnormalities of the uterus, genital diseases of endometriosis and inflammatory diseases, and immunological factors. Accounted for. Gynecologically, most obese women are known to have high concentrations of gonadotrophin and high male hormone, Androgen, which results in hypertrophy of the ovary and few follicles on the surface of the ovary. This can lead to abnormal ovarian function, which causes rare ovulation, non-menstruation, and malfunctioned vaginal hemorrhage in obese women. It may also result. Gynecologically, most obese women have high levels of gonadotrophin and high Androgen, and are known to have ovary hypertrophy and small follicles on the surface of the ovary. Obese women underwent a low calorie diet and weight loss to observe the effects of obesity on menstruation. In the group with weight loss, the menstrual cycle was restored normally, and pregnancy was possible in obese women who failed to lose weight. Menstruation did not recover normally. Androgen hyperactivity and ovulation have been shown to successfully treat infertility due to weight loss in obese women diagnosed with polycystic ovary syndrome. The figures returned to normal. In addition, excessive weight may cause the implantation of the fertilized egg to fail, which may cause problems with the endometrium. Therefore, it can be seen that weight loss is an effective treatment method because the reproductive function abnormalities caused by the change of sex hormone dynamics in obese women are corrected.
이에 본 발명자들은 생쥐를 이용한 실험으로부터 비만으로 인한 월경불순 및 배란장애, 난소이상에 대해 효과적인 물질로써 고분자 수용성 키토산을 발견하였으며 이는 체지방 감소로 인한 내분비 및 대사기능의 정상적 조정능력의 회복, 난소기능을 비롯한 생식기능의 향상에 효과가 있다는 사실을 발견하였다.The present inventors have found a macromolecular water-soluble chitosan as an effective substance against menstrual irregularity, ovulation disorders and ovarian abnormalities due to obesity from experiments with mice, which restores normal control ability of endocrine and metabolic function due to body fat reduction, and ovarian function. It has been found to be effective in improving reproductive function.
고분자 수용성 키토산 제조방법Manufacturing Method of Polymer Water Soluble Chitosan
새우 및 게의 껍질로부터 얻은 키토산을 산으로 처리한 후 키토시나아제, 키티나제, 셀롤라제 및 라이소자임 중 어느 하나 이상의 효소를 0.1내지 15중량%의 농도로 처리하여 수용화 시켰다. 상기 효소처리와 병행하여, 10∼40KHz 범위의 주파수에서 시간 20∼90분간 초음파 처리하였다.Chitosan obtained from the shells of shrimps and crabs was treated with acid, and then subjected to any one or more enzymes of chitocinase, chitinase, celolase, and lysozyme at a concentration of 0.1 to 15% by weight. In parallel with the enzyme treatment, sonication was performed for 20 to 90 minutes at a frequency in the range of 10-40 KHz.
그 다음 진공 건조 시킨 후 순수한 물에 용해 시켜, 상기와 같은 초음파 공정을 반복적으로 수행한 다음 정제하여 22만∼100만 범위의 평균분자량을 갖는 키토산 혼합물을 얻었다. 그 후 상기 혼합물을 냉동건조시켜 인체에 흡수될 수 있는 수용성 고분자 키토산을 제조하였다. 이와 같이 하여 제조된 수용성 고분자 키토산을 분자량에 따라 나누면 하기 표1과 같다.Thereafter, the resultant was dried in vacuo and then dissolved in pure water. The ultrasonic process was repeated and purified to obtain a chitosan mixture having an average molecular weight in the range of 220,000 to 1 million. Thereafter, the mixture was lyophilized to prepare a water-soluble polymer chitosan that can be absorbed by the human body. The water-soluble polymer chitosan prepared in this manner is divided into the following Table 1 by molecular weight.
또한 새우 및 게로부터 얻은 키토산에 키토사나아제를 키토산에 대하여 5 중량%로 주입함과 동시에 각각 10, 20 및 30KHz로 20, 30, 60및 90분간 초음파 처리하여 얻어진 키토산의 평균 분자량은 하기 표2와 같다.In addition, chitosan obtained from shrimp and crab was injected with chitosanase at 5% by weight relative to chitosan, and the average molecular weight of chitosan obtained by sonication at 20, 30, 60 and 90 minutes at 10, 20 and 30 kHz, respectively, is shown in Table 2 below. Same as
상기와 같은 평균 분자량을 갖는 키토산을 제조한후 냉동건조하여 불순물이 없는 평균 분자량 220,000∼1,000,000인 키토산을 얻었다. 분자량은 GPC (gel permeation Chromatography)로 측정하였다.Chitosan having an average molecular weight as described above was prepared and freeze-dried to obtain chitosan having an average molecular weight of 220,000 to 1,000,000 without impurities. Molecular weight was measured by GPC (gel permeation Chromatography).
상기 실시예 1 내지 실시예6의 제조공정으로 얻어진 최종제품의 중금속(Pb, As)을 정량 분석 하였다. 납(Pb)과 비소(As)의 정량은 자동흡수 스펙트럼(Atomic absorption spectrometer)(Varian Co. spectraAA-300, USA)을 사용하여 정량해본 바, 매우 양호한 구성물임을 확인 하였다.Heavy metals (Pb, As) of the final product obtained in the manufacturing process of Example 1 to Example 6 were quantitatively analyzed. Determination of lead (Pb) and arsenic (As) was carried out using an atomic absorption spectrometer (Varian Co. spectra AA-300, USA), and found to be a very good component.
또한 초음파공법을 통해 얻어진 고분자 수용성 키토산의 황산화 효과를 대표적인 황산화물인 비타민 C와 비교하였다. 상기 실시예 1 내지 실시예 6의 최종산물을 용액으로 제조하여 실험 하였으며 , 표3에서와 같이 안정한 상태와 우수한 황산화력을 나타내었다. 측정은 UV흡광기(Cary Ⅰ. UV-Visible Spectrophotometer.: Vanan Co. USA)로 하였다.In addition, the sulfated effect of the polymer water-soluble chitosan obtained through the ultrasonic method was compared with the representative sulfur oxide vitamin C. The final product of Example 1 to Example 6 was prepared as a solution and tested, and showed a stable state and excellent sulfate power as shown in Table 3. The measurement was carried out with a UV absorber (Cary I. UV-Visible Spectrophotometer .: Vanan Co. USA).
실험예 1 : 고분자 수용성 키토산이 비만 생쥐의 체중감량에 미치는 효과Experimental Example 1 Effect of Polymer Soluble Chitosan on Weight Loss in Obese Mice
부인과적으로 비만여성은 대부분 혈중성선자극호르몬 (gonadotrophin)의 농도가 높아 Androgen분비가 높고, 난소(ovary)비대와 난소표면에 적은 난포(follicle)가 존재하는 것으로 알려져 있다. 먼저 체지방 감소에 이물질이 효과가 있는지를 알아보기 위해 실시예1에서 제조된 고분자 수용성 키토산을 생쥐에 투여해서 체지방을 감소시키는지에 대한 실험을 실시하였다. 비만으로 인해 배란장애 및 월경불순, 난소기능이상이 발생한다는 것을 감안한다면 비만을 치유하는 약물을 후보물질로 설정하고 그 후보 물질은 불임치료에도 효과가 있을 가능성이 있을 것으로 보고 본 연구는 추진되었다. 이에 본 발명자들은 비만 체중군은 고단백, 고지방사료와 고밀도 사육으로 비만을 유도한 생쥐 중 체중이 27g 이상으로 비만이 유도된 실험군과 대조군을 설정하였다. 정상 체중군은 정상 사료와 저밀도 사육을 실시해 체중이 22g이하인 생쥐를 실험군과 대조군으로 설정하였다. 실험군은 수용성 키토산(32mg/㎖)을 1일 1회 0.3㎖씩 4일간 투약하고 대조군은 물을 1일 1회 0.3㎖씩 4일간 투여하였다(table 1). 키토산과 물을 각각 4일간 투여 후 4일간 휴식을 시킨 후 각각 실험군과 대조군의 평균체중변화를 측정하였다.Gynecologically, most obese women are known to have high levels of gonadotrophin and high Androgen secretion, and ovary hypertrophy and few follicles on the surface of the ovary. First, in order to determine whether the foreign body is effective in reducing body fat, an experiment was performed to reduce body fat by administering the polymer-soluble chitosan prepared in Example 1 to mice. Considering that obesity causes ovulation disorders, menstrual disorders, and ovarian dysfunction, a drug that cures obesity is considered as a candidate substance, and the candidate substance may be effective in infertility treatment. The present inventors set the experimental group and the control group obesity-induced body weight over 27g of the obese body weight-induced obesity in the high protein, high fat feed and high-density breeding. In the normal weight group, mice with a body weight of 22g or less were subjected to normal feeding and low-density rearing as the experimental group and the control group. The experimental group administered water-soluble chitosan (32 mg / ml) once daily for 0.3 ml for 4 days and the control group received water 0.3 ml once daily for 4 days (table 1). Chitosan and water were each administered for 4 days and then rested for 4 days, and then the average weight change of the experimental and control groups was measured.
실험결과 고단백과 고지방사료 및 고밀도 사육된 생쥐 중 27g 이상인 비만체중군의 경우 대조군에서 평균체중이 1.73g증가한 반면 키토산을 구강 투여한 실험군에서 평균체중이 4.50g감소되어 유의성 있는 체중감소효과를 나타내었으며 한편, 정상사료와 저밀도 사육된 생쥐 중 22g이하인 정상체중군의 경우 대조군에서 평균체중이 1.50g 증가한 반면 키토산을 투여한 실험군에서는 평균체중이 0.90g 증가되어 상대적으로 유의성 있는 체중감소효과를 나타내었다(table 2). 이러한 결과는 고분자 수용성 키토산이 체내에 축적되어 있는 체지방을 감소시켰기 때문일 것으로사료된다.As a result, the obese body weight group over 27g among the high protein, high fat diet and high-density reared mice showed 1.73g increase in the control group, while the mean weight loss decreased 4.50g in the chitosan oral administration group. On the other hand, the normal weight group of 22g or less of normal feed and low-density reared mice showed 1.50g increase in mean weight in the control group, while 0.90g increase in mean weight in the experimental group treated with chitosan, indicating a significant weight loss effect. table 2). These results may be due to the fact that the polymer water-soluble chitosan reduced body fat accumulated in the body.
실험예 2: 고분자 수용성 키토산 투약이 비만생쥐의 배란율에 미치는 효과Experimental Example 2: Effect of Polymer Water Soluble Chitosan Administration on Ovulation Rate in Obese Mice
키토산과 물을 4일간 투여후 4일간 휴식한 후 각각 실험군과 대조군의 암컷 생쥐에 5 IU의 PMSG(Pregnant Mare's Seru Gonadotropin; 임마혈청 성선자극호르몬)를 복강내 주사한 뒤 48시간 후에 5IU의 hCG(Human Chorionic Gonadotropin;임부태반융모성 성선자극 호르몬)를 복강 내 주사함으로써 과배란(superovulation)을 유도하였다. PMSG와 hCG를 이용하여 과배란을 유도한 생쥐를 hCG투여 후 경추탈골법 (Cervical dislocation method)으로 생쥐를 도살한 후 난관을 적출 하였다. 적출된 난관은 해부현미경 하에서 난관 팽대부에 배란된 난자-난구세포 복합체를 회수하여 실험군과 대조군 각각 배란된 난자의 총수와 형태학적으로 정상인 난자의 수를 조사하였다.After 4 days of administration of chitosan and water, the rats were rested for 4 days, and then 5 hours of 5IU of hCG Superovulation was induced by intraperitoneal injection of Human Chorionic Gonadotropin (pregnant placental chorionic gonadotropin). Hyperovulation-induced mice were treated with PMSG and hCG, and the fallopian tubes were extracted after slaughter of the mice by cervical dislocation method after hCG administration. The isolated oviducts were recovered under the dissecting microscope, and the oocyte-oocyte complexes ovulated in the oviductal bulge were collected to investigate the total number of ovulated eggs and the number of morphologically normal eggs in the experimental and control groups.
실험결과 27g 이상인 비만군에서는 배란된 생쥐의 평균난자수가 실험군은 대조군에 비해 14.3% 배란율 증가를 나타내었고, 22g 이하인 정상군에서도 역시 실험군이 대조군보다 10.6% 증가를 나타내었다.As a result, in the obese group of 27g or more, the number of ovulated mice showed an increase of 14.3% ovulation rate compared to the control group, and the experimental group also showed a 10.6% increase in the normal group of 22g or less.
배란된 난자 중 정상난자의 수에 있어서는 비만군의 경우 키토산을 투여한 실험군이 대조군에 비해 9.2%증가를 나타내었으나 정상군에서는 실험군과 대조군에서 유의성 있는 차이가 없었다(table 3). 이러한 결과는 고분자 수용성 키토산이 체중감량에 따른 배란율에 영향을 미친다는 것을 보여준다.In obese group, chitosan-treated group showed 9.2% increase in the number of normal eggs in ovulated group, but there was no significant difference between normal group and control group (Table 3). These results show that the polymer-soluble chitosan affects the ovulation rate according to weight loss.
실험예 3: 체외수정과 배발생에 있어서 고분자 수용성 키토산의 효과Experimental Example 3: Effect of Polymer Water Soluble Chitosan on In Vitro Fertilization and Embryogenesis
비만군과 정상군의 실험군과 대조군을 각각 선정하여 키토산과 물을 각각 4일간 투여 후 4일간 휴식기를 보낸 생쥐에게 PMSG와 hCG를 각각 5IU씩 48시간 간격으로 복강내에 주사하여 과배란을 유도하고 과배란 유도 직후 자성생쥐를 생식능력이 확인된 웅성생쥐와 1:1 비율로 합사하여 교미를 유도하였다. 익일 아침 자성 생쥐의 질전(veginal plug)유무를 통하여 교미여부를 확인하였고, 질전이 확인된 개체만을 골라 실험에 이용하였다. 선택된 개체에 hCG투여후 경추탈골법으로 도살하고 난관을 적출하여 1-세포기 수정란만을 선별하였다. 이 수정란을 배양액에 옮겨 37℃, 5% CO2배양기에서 배양하면서 수정란의 배발생을 관찰하였다.The experimental and control groups of the obese and normal groups were selected for 4 days of chitosan and water, respectively, and 4 hours after resting for 4 days. Female mice were mated 1: 1 with male rats whose fertility was confirmed to induce mating. The following morning, mating was confirmed by the presence or absence of a vaginal plug in the magnetic mice, and only the individuals whose vagina was confirmed were used for the experiment. After hCG administration, selected individuals were slaughtered by cervical dislocation and the oviducts were extracted to select only 1-cell fertilized eggs. The embryos were transferred to a culture solution and cultured in a 37 ° C., 5% CO 2 incubator to observe embryonic development.
이 결과 수정된 난자의 비율은 체중이 27g이상인 비만군의 경우, 실험군이 대조군에 비해 10.4% 증가했으며, 체중이 22g이하인 정상군에서도 실험군이 대조군에 비해 유의성 있게 높게 나타났다. 배발생에 있어서도 비만군의 경우, 키토산을 투여한 실험군이 대조군에 비해 33.9% 증가했으며, 정상군에서도 역시 실험군이 대조군에 비해 2.0% 증가율을 보였다(table 4). 이러한 결과는 고분자 수용성 키토산이 체내 지방을 감소시켜 난소기능을 비롯한 생식기능을 정상적으로 향상시켰기 때문일 것으로 보여진다.As a result, the percentage of fertilized eggs was increased by 10.4% compared to the control group in the obese group weighing more than 27g, and the experimental group was significantly higher than the control group in the normal group with weight less than 22g. In embryonic development, in the obese group, the experimental group administered chitosan increased by 33.9% compared to the control group, and in the normal group, the experimental group also showed a 2.0% increase compared to the control group (Table 4). These results may be due to the fact that the polymer water-soluble chitosan reduced fat in the body and normally improved reproductive function including ovarian function.
실험예 4 : 키토산을 농도별로 난자내 직접 투여 후 배발생에 미치는 효과Experimental Example 4 Effects of Chitosan on Embryogenesis after Direct Administration in Oocytes by Concentration
Table 4에서 본바와 같이 수용성 키토산이 구강투여 되었을 때 체내수정과 배발생에 영향이 있는 것으로 사료되나 체내의 다양한 환경과 같은 여러 변수들을 배제함과 아울러 체내의 배란 촉진효과가 체외에서도 직접 나타나는지를 증명하기 위해 수정된 난자 안으로 미세조작기를 이용해 고분자 수용성 키토산을 다양한 농도로 직접 주입한 후 키토산이 배발생에 미치는 효과에 대해 실험하였다. 실험결과 체중이 27g이상인 비만군에서는 대조군과 비교시 실험군에서 300ng 농도를 처리시에 88.6%로 유의성 있는 증가를 보였으며, 그림3과 비교시 배발생율의 증가를 알 수 있었다. 또, 체중이 22g이하인 정상군에서는 대조군과 비교시 실험군에서 유의성 있는 차이를 나타내지 않았다(table 5). 이 결과 고분자 수용성 키토산은 생쥐에 키토산을 구강투여 후 체외수정과 배발생율을 증진시킨다는 사실이 수정된 난자에 키토산을 직접 주입하는 본 실험에서도 그 효과가 증명되었다.As shown in Table 4, when water-soluble chitosan is orally administered, it is thought to have an effect on fertilization and embryonic development, but it excludes various variables such as various environments in the body and proves whether the effect of promoting ovulation in the body is directly expressed in vitro. In order to directly inject the polymer water-soluble chitosan at various concentrations using a micromanipulator into the fertilized egg, the effects of chitosan on embryonic development were tested. As a result, the obese group weighing more than 27g showed a significant increase of 88.6% when treated with 300ng concentration in the experimental group compared with the control group. In addition, the normal group of less than 22g body weight did not show a significant difference in the experimental group compared to the control group (table 5). As a result, it was demonstrated that the polymer-soluble chitosan enhances in vitro fertilization and embryonic development after oral administration of chitosan to mice.
이상의 동물 실험에서 알 수 있는 바와 같이 본 발명물은 현재 아시아에서 2번째의 비만국이고 이로 인해 국민건강이 위협받고 있는바 국민의 체지방 감소효과와 비만으로 인한 배란장애 및 월경불순, 배란장애의 치료 및 예방 식·의약품으로서 유용하게 사용될 수 있을 것으로 기대된다.As can be seen from the above animal experiments, the present invention is the second obese country in Asia, which threatens the public's health. As a result, the treatment of ovulation disorders, menstrual disorders and ovulation disorders caused by obesity reduction effect of body fat and obesity And it is expected that it can be usefully used as a preventive food and pharmaceutical.
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| JPH06321786A (en) * | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | Agent for inhibiting absorption of bile acid in enteric canal |
| JPH06321787A (en) * | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | Carbohydrate absorption-inhibiting agent |
| US5654001A (en) * | 1992-03-24 | 1997-08-05 | Kirin Beer Kabushiki Kaisha | Dietary lipid digestion-absorption inhibitory agents and ingesta |
| WO1998034625A1 (en) * | 1997-02-06 | 1998-08-13 | Novasso Oy | Substance and method for reduction of lipids and cholesterol |
| JPH11147828A (en) * | 1997-11-17 | 1999-06-02 | Koji Kashima | Absorption inhibitor against cholesterol and lipid |
| KR20010085047A (en) * | 2001-07-25 | 2001-09-07 | 장태순 | Inhibitory Effect of Body Fat Gain by a High-Fat Diet of High Molecular Weight Water-soluble Chitosan |
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| US5654001A (en) * | 1992-03-24 | 1997-08-05 | Kirin Beer Kabushiki Kaisha | Dietary lipid digestion-absorption inhibitory agents and ingesta |
| JPH06321786A (en) * | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | Agent for inhibiting absorption of bile acid in enteric canal |
| JPH06321787A (en) * | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | Carbohydrate absorption-inhibiting agent |
| WO1998034625A1 (en) * | 1997-02-06 | 1998-08-13 | Novasso Oy | Substance and method for reduction of lipids and cholesterol |
| JPH11147828A (en) * | 1997-11-17 | 1999-06-02 | Koji Kashima | Absorption inhibitor against cholesterol and lipid |
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