CN1698883A - Application of nerve growth factor in preparation of medicine for effective reducing body weight - Google Patents
Application of nerve growth factor in preparation of medicine for effective reducing body weight Download PDFInfo
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- CN1698883A CN1698883A CN 200410042552 CN200410042552A CN1698883A CN 1698883 A CN1698883 A CN 1698883A CN 200410042552 CN200410042552 CN 200410042552 CN 200410042552 A CN200410042552 A CN 200410042552A CN 1698883 A CN1698883 A CN 1698883A
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- 108010025020 Nerve Growth Factor Proteins 0.000 title claims abstract description 39
- 229940053128 nerve growth factor Drugs 0.000 title claims abstract description 38
- 239000003814 drug Substances 0.000 title claims abstract description 23
- 102000015336 Nerve Growth Factor Human genes 0.000 title claims abstract 9
- 230000037396 body weight Effects 0.000 title abstract description 24
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 239000007922 nasal spray Substances 0.000 claims description 8
- 229940097496 nasal spray Drugs 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 2
- 210000002850 nasal mucosa Anatomy 0.000 claims 2
- 210000001331 nose Anatomy 0.000 claims 2
- 239000000843 powder Substances 0.000 claims 2
- 206010028748 Nasal obstruction Diseases 0.000 claims 1
- 239000000443 aerosol Substances 0.000 claims 1
- 239000007923 nasal drop Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 241000700159 Rattus Species 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 5
- 239000013585 weight reducing agent Substances 0.000 abstract 2
- 230000002411 adverse Effects 0.000 abstract 1
- 238000001647 drug administration Methods 0.000 abstract 1
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 30
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 235000019786 weight gain Nutrition 0.000 description 5
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- 210000003928 nasal cavity Anatomy 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229960001582 fenfluramine Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000021479 Cardiovascular injury Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010017999 Gastrointestinal pain Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000634196 Homo sapiens Neurotrophin-3 Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 102100029268 Neurotrophin-3 Human genes 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
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- 206010022437 insomnia Diseases 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 210000000933 neural crest Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 210000001913 submandibular gland Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses the use of nerve growth factor in preparation of medicine for effective reducing body weight, wherein the advantages of the invention are, (1) effective weight reduction, the nerve growth factor can directly inhibit the weight increase for rats, and no rebounding of weight is produced after drug administration, (2) no appreciable adverse effects, no habit-forming result. Therefore, the nerve growth factor can be effectively used for weight reduction.
Description
Technical field
The present invention relates to the application of nerve growth factor in the effective slimming medicine of preparation, belong to biomedicine field.
Background technology
Body weight is by the relative equilibrium decision of food intake and energy expenditure, though factors such as heredity can cause fat, but the common cause of weight increase and physiological obesity is to take in too high heat and/or energy expenditure reduces, and the excess fat that causes is thus piled up the sickness rate of cardiovascular and cerebrovascular vessel such as can increasing hypertension, hyperlipidemia, non-insulin-dependent diabetes mellitus, coronary heart disease, sleep apnea syndrome to overweight or obese people and respiratory system disease.
Can partly lose weight or prevent obesity by diet, behavior change and medicine, medicine commonly used has orlistat, can reduce fat content from the diet of intestinal absorption; Sibutramine is by suppressing the reuptake appetite-suppressing of norepinephrine and 5-hydroxy tryptamine; Fenfluramine is by discharging 5-hydroxy tryptamine and suppressing the reuptake appetite-suppressing of 5-hydroxy tryptamine subsequently.But slightly to the untoward reaction of severe, for example, fenfluramine is through the remarkable risk that increases cardiovascular injury of clinical proof meeting for most medicines, and U.S. FDA was removed the city in 1999 with it.The common adverse reactions of other medicine that loses weight comprises giddy, headache, cardiopalmus, insomnia, diarrhoea, intestinal spasm and hypertension etc.Except that untoward reaction, many lose weight medicine for example amphetamine also have addiction.
Nerve growth factor NGF is a kind of neurocyte regulatory factor of being found in mouse tumor cell in nineteen fifty-three by Italian embryologist Rita Levi-Montalcini and Americanized scholar StanleyCohen, its main source is the target cell of neural crest neuron domination, neurogliocyte as maincenter, the schwann cell of periphery, skeletal muscle and some bodies of gland; Adult mice submaxillary gland, cattle seminal fluid, snake venom and people's Placenta Hominis all contain abundant NGF.
Over more than 50 year, the countries in the world scholar is deepening continuously and is expanding the research of NGF, finds that NGF has obvious effect to nerve injury and immune system and other system, but animal and human's body is not seen obvious toxic and side effects as yet.
At present domesticly be mainly used in the treatment of brothers' nerve injury, alzheimer disease, neural graft, cerebral ischemia diseases, tip peripheral neuritis etc. as the medicine of Main Ingredients and Appearance listing, but do not see that the fat report of NGF treatment is arranged with NGF.
Summary of the invention
The object of the present invention is to provide the application of nerve growth factor in the effective slimming medicine of preparation.
For achieving the above object, the present invention is by the following technical solutions:
The application of nerve growth factor in the effective slimming medicine of preparation.
We find in the research that NGF is carried out, and use NGF2 after week to rat, and the body weight gain of rat is not obvious, and is dependence with dosage; After 4 weeks of administration, the phenomenon that this body weight does not increase still exists, so we test at this situation, and has found NGF can be used for the losing weight beyond thought effect of function.
Advantage of the present invention is: 1) effectively lose weight: compare with present slimming many medicines, nerve growth factor can directly suppress the growth of rat body weight, stop administration after body weight do not rebound; 2) no obvious adverse reaction: compare with existing medicine, do not find in this research that nerve growth factor has tangible untoward reaction, no addiction.Therefore utilize nerve growth factor effectively to lose weight, have good society and market prospect.
The invention will be further described below in conjunction with the specific embodiment, do not limit the scope of protection of the invention with this.
The specific embodiment
Embodiment 1
Present embodiment is prepared into injection and nasal spray with NGF, and rat is carried out administration, subsequently its body weight is observed, and confirms the inhibitory action of NGF to body weight gain.
1, medicine
Nerve growth factor (NGF) injection, nasal spray (the clear new drug research development centre of spreading out, Beijing provides)
2. animal
Wister rat (purchasing Experimental Animal Center) in Military Medical Science Institute, 40, male, the standard beverage is fed;
Respectively to rat muscle injection, nasal spray administration, 4000 units/kg body weight, the blank group be normal raising.2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks and 15 weeks are measured rat body weights when treatment and after the treatment.
3, experimental result: table 1 NGF is to the influence of male rat body weight
| Test week | Body weight (x ± SD, g) | ||
| Matched group | The intramuscular injection group | The nasal-cavity administration group | |
| ??W0 ??W2 ??W4 ??W6 ??W8 ??W10 ??W12 ??W15 △ | ??179.8±13.7 ??282.5±23.6 ??339.9±28.8 ??392.0±36.4 ??422.3±39.8 ??458.2±42.0 ??454.5±43.7 ??505.00±58.3 | ??170.0±8.9 ??255.9±21.4 **??312.0±29.9 **??358.0±39.1 **??389.8±44.5 *??422.6±46.9 *??413.3±45.2 ??463.00±81.0 | ??174.0±13.3 ??226.3±17.1 **??270.5±23.8 **??334.5±32.0 **??365.1±40.3 **??398.8±47.6 **??407.0±46.6 **??444.00±36.3 |
N=20,
*P＜0.05,
*Compare with the concurrent control group p＜0.01, and significant difference, △ are convalescent period, n=5.
Table 2 NGF is to the influence of male rat body weight gain
| Test week | Body weight (x ± SD, g/d/ are only) | ||
| Matched group | The intramuscular injection group | The nasal-cavity administration group | |
| ??W0～W2 ??W2～W4 ??W4～W6 ??W6～W8 ??W8～W10 ??W10～W12 ??W12～W15 △ | ??6.16±1.49 ??4.52±1.D95 ??2.90±1.15 ??2.02±2.04 ??2.22±0.82 ??-0.61±5.32 ??1.41±0.46 | ??5.06±1.25 *??4.32±1.29 ??2.56±1.20 ??2.12±0.62 ??2.05±0.98 ??-0.68±1.82 ??1.51±0.76 | ??3.08±0.79 *??3.40±1.74 ??3.56±1.39 ??2.37±0.68 ??1.73±1.41 ??1.15±2.77 ??2.06±0.66 |
N=20,
*P＜0.05,
*Significant difference is compared with the concurrent control group in p＜0.01.△n＝5。
Embodiment 2
Present embodiment is prepared into injection and nasal spray with NGF, and rat is carried out administration, subsequently its body weight is observed, and confirms the inhibitory action of NGF to body weight gain.
1, medicine
Nerve growth factor (NGF) injection, nasal spray (the clear new drug research development centre of spreading out, Beijing provides)
2, animal
Wister rat (purchasing Experimental Animal Center) in Military Medical Science Institute, 40, female, the standard beverage is fed;
Respectively to rat muscle injection, nasal spray administration, 4000 units/kg body weight, the blank group be normal raising.2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks and 15 weeks are measured rat body weights when treatment and after the treatment.
3, experimental result: see Table 3 and table 4.
Use mentioned nerve growth factor injection of the present invention and nasal spray can prevent that rat body weight from increasing, effect has dose dependent.Rat is used the slimming test bay of nerve growth factor preparation, does not find tangible untoward reaction, and convalescent period is not found any untoward reaction yet, so nerve growth factor is a kind of new effectively losing weight and do not have the medicine of obvious adverse reaction.
Table 3 NGF is to the influence of female rats body weight
| Test week | Body weight (x ± SD, g) | ||
| Matched group | The intramuscular injection group | The nasal-cavity administration group | |
| ??W0 ??W2 ??W4 ??W6 ??W8 ??W10 ??W12 ??W15 △ | ??170.2±10.4 ??227.2±11.0 ??256.5±10.9 ??276.5±17.9 ??290.1±26.3 ??295.1±21.6 ??306.2±25.6 ??321.00±39.3 | ??171.5±11.2 ??226.8±17.1 ??256.8±20.8 ??288.0±30.9 ??295.4±29.1 ??305.5±30.2 ??317.8±30.1 ??322.0±32.9 | ??163.9±11.4 ??203.0±14.2 **??234.0±15.2 **??265.0±23.3 ??278.5±26.5 ??293.2±30.7 ??300.6±27.3 ??316.00±36.6 |
N=20,
*P＜0.05,
*Significant difference, △ n=5 are compared with the concurrent control group in p＜0.01.
Table 4 NGF is to the influence of female rats body weight gain
| Test week | Body weight (x ± SD, g/d/ are only) | ||
| Matched group | The intramuscular injection group | The nasal-cavity administration group | |
| ??W0～W2 ??W2～W4 ??W4～W6 ??W6～W8 ??W8～W10 ??W10～W12 ??W12～W15 △ | ??3.45±0.93 ??2.25±0.91 ??1.14±0.71 ??0.83±0.97 ??0.33±0.83 ??1.10±1.02 ??0.78±0.38 | ??3.32±0.67 ??2.39±1.12 ??1.62±1.56 ??0.50±1.81 ??0.32±1.11 ??1.19±1.10 ??0.86±0.43 | ??2.30±0.84 **??2.39±0.80 ??1.72±0.72 *??1.03±0.62 ??0.80±0.54 *??0.89±1.49 ??0.92±1.05 |
N=20,
*P＜0.05,
*Significant difference, △ n=5 are compared with the concurrent control group in p＜0.01.
Claims (4)
1, the application of nerve growth factor in the effective slimming medicine of preparation.
2, nerve growth factor according to claim 1 is characterized in that in the application of preparation in effective slimming medicine: described nerve growth factor is an injection or through the nasal mucosa medicine administration dosage form.
3, the application of nerve growth factor according to claim 2 in the effective slimming medicine of preparation, it is characterized in that: described injection comprises solution type injection agent, suspension type injection, emulsion-type injection, injection freeze-dried powder and injectable sterile powder.
4, nerve growth factor according to claim 2 is characterized in that in the application of preparation in effective slimming medicine: describedly comprise that through the nasal mucosa medicine administration dosage form nasal spray, nasal drop, nose are with solution, nasal obstruction agent and nose aerosol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100425525A CN100413535C (en) | 2004-05-21 | 2004-05-21 | Application of nerve growth factor in preparation of medicine for effective reducing body weight |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100425525A CN100413535C (en) | 2004-05-21 | 2004-05-21 | Application of nerve growth factor in preparation of medicine for effective reducing body weight |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1698883A true CN1698883A (en) | 2005-11-23 |
| CN100413535C CN100413535C (en) | 2008-08-27 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016169455A1 (en) * | 2015-04-21 | 2016-10-27 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor composition and powder injection |
| WO2017157325A1 (en) * | 2016-03-18 | 2017-09-21 | 舒泰神（北京）生物制药股份有限公司 | Fusion protein comprising nerve growth factor and preparation method and use thereof |
| CN107286233A (en) * | 2016-04-13 | 2017-10-24 | 舒泰神（北京）生物制药股份有限公司 | Low pain nerve growth factor mutant |
| CN109395084A (en) * | 2018-11-14 | 2019-03-01 | 威海市千谷生物科技有限公司 | A kind of fat melting line and fat melting liquid and the method for weight-reducing of sunkening cord using it |
-
2004
- 2004-05-21 CN CNB2004100425525A patent/CN100413535C/en not_active Expired - Lifetime
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016169455A1 (en) * | 2015-04-21 | 2016-10-27 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor composition and powder injection |
| CN114671941A (en) * | 2016-03-18 | 2022-06-28 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor mutant |
| EP3431494A4 (en) * | 2016-03-18 | 2020-01-01 | Staidson(Beijing) Biopharmaceuticals Co., Ltd. | Nerve growth factor mutant |
| CN109071678A (en) * | 2016-03-18 | 2018-12-21 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor fusion protein, preparation method and its usage |
| CN109153709A (en) * | 2016-03-18 | 2019-01-04 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor mutant |
| US11213568B2 (en) | 2016-03-18 | 2022-01-04 | Staidson (Beijing) Biopharmaceuticals Co., Ltd. | Nerve growth factor mutant |
| EP3431507A4 (en) * | 2016-03-18 | 2019-08-14 | Staidson(Beijing) Biopharmaceuticals Co., Ltd. | Fusion protein comprising nerve growth factor and preparation method and use thereof |
| EP4292649A3 (en) * | 2016-03-18 | 2024-02-21 | Staidson(Beijing) Biopharmaceuticals Co., Ltd. | Fusion protein comprising nerve growth factor and preparation method and use thereof |
| US11883464B2 (en) | 2016-03-18 | 2024-01-30 | Staidson (Beijing) Biopharmaceuticals Co., Ltd. | Nerve growth factor fusion protein, preparation method and use thereof |
| CN114671941B (en) * | 2016-03-18 | 2023-09-26 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor mutant |
| CN109071678B (en) * | 2016-03-18 | 2022-05-20 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor fusion protein, preparation method and application thereof |
| CN109153709B (en) * | 2016-03-18 | 2022-05-27 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor mutant |
| WO2017157325A1 (en) * | 2016-03-18 | 2017-09-21 | 舒泰神（北京）生物制药股份有限公司 | Fusion protein comprising nerve growth factor and preparation method and use thereof |
| CN114671942A (en) * | 2016-03-18 | 2022-06-28 | 舒泰神（北京）生物制药股份有限公司 | Nerve growth factor mutant |
| CN107286233B (en) * | 2016-04-13 | 2020-11-06 | 舒泰神（北京）生物制药股份有限公司 | Low-pain nerve growth factor mutant |
| CN107286233A (en) * | 2016-04-13 | 2017-10-24 | 舒泰神（北京）生物制药股份有限公司 | Low pain nerve growth factor mutant |
| CN109395084A (en) * | 2018-11-14 | 2019-03-01 | 威海市千谷生物科技有限公司 | A kind of fat melting line and fat melting liquid and the method for weight-reducing of sunkening cord using it |
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| Publication number | Publication date |
|---|---|
| CN100413535C (en) | 2008-08-27 |
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