CN101804075B - Application of starfishes to preparation of medicament for treating osteoporosis - Google Patents

Application of starfishes to preparation of medicament for treating osteoporosis Download PDF

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CN101804075B
CN101804075B CN2010101550922A CN201010155092A CN101804075B CN 101804075 B CN101804075 B CN 101804075B CN 2010101550922 A CN2010101550922 A CN 2010101550922A CN 201010155092 A CN201010155092 A CN 201010155092A CN 101804075 B CN101804075 B CN 101804075B
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asterias amurensis
asterias
amurensis lutken
osteoporosis
preparation
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CN101804075A (en
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张成海
周文波
李冬梅
石桂芳
姜伟
黄积辉
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DALIAN MERRO PHARMACEUTICAL Co Ltd
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DALIAN MERRO PHARMACEUTICAL Co Ltd
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Abstract

The invention discloses the application of starfishes to the preparation of a medicament for treating osteoporosis. The application of the starfishes is realized by steaming, drying, cooling and crushing Chinese medical starfish herbs, such as asterias rollestoni and asterias amurensis from asteriidae animals or Dow sun starfish from solasteridae animals, preparing and orally administrating. Proved by research, the starfishes have the functions of stimulating the growth of sclerotomal cells, promoting the pigmentation, enhancing the bone density, and the like and have remarkable effect of treating the osteoporosis. The medicament for treating osteoporosis, which is prepared by the technical scheme, has the advantages of good treatment, high effect taking, high curative effect without any side effect, and the like during clinical applications and has sufficient drug resources, simple preparation method and low cost.

Description

The application of Asterias amurensis Lutken in the medicine of preparation treatment osteoporosis
Technical field
The present invention relates to the new purposes of Chinese medicine Asterias amurensis Lutken, especially the application in the medicine of preparation treatment osteoporosis.
Background technology
Osteoporosis (osteoporosis) is that a kind of microstructure degeneration with the minimizing of bone amount, bone is the systemic skeletal diseases of characteristic; Clinical manifestation is that the fragility of bone increases; Therefore the dangerous of fracture greatly increase, even also fracture easily under slight wound or the atraumatic situation.
There are 200,000,000 sufferers of osteoporosis face in the whole world, and the senile osteoporosis sickness rate is higher, and the women is more than the male.Standard according to World Health Organization (WHO); American National health and nutritional survey result show; Osteoporosis has a strong impact on the life of elderly person quality, and among the crowd, 1/2 women, 1/5 male osteoporotic fracture can occur in life more than 50 years old; In case patient experience osteoporotic fracture for the first time, the dangerous of secondary fracture obviously strengthened.China old people occupy first place, the world, and existing patients with osteoporosis 9,000 ten thousand accounts for 7.1% of total population.Aggravation along with aged tendency of population; The sickness rate of osteoporosis is in rising trend; Expect the year two thousand fifty China's patients with osteoporosis and will be increased to 2.21 hundred million; Whole world osteoporotic fracture over half will occur in the Asia at that time, and the overwhelming majority is in China, and the medical expense of the miscellaneous fracture that osteoporosis caused will become the heavy financial burden of China's health medical insurance system undoubtedly.
Join imbalance to osteoporosis patient bone resorption and bone formation corner, western medicine is divided into three major types:
1. bone resorption inhibitor can suppress the activity of osteoclast, reduces the loss of bone calcium, and main medicine has diphosphonate, estrogen, calcitonin, estrogenic agents etc.;
2. bone formation-promoter can directly stimulate bone formation, obviously improves bone density, and medicine comprises fluoride, parathyroid hormone, strontium salt, growth hormone etc.;
3. bone mineralising promoter promotes the bone calcific deposit, increases the bone amount, and this type medicine has vitamin D and calcium preparation.
Though the western medicine osteoporosis has obtained certain curative effect, side effect is big, and costs an arm and a leg.As after taking hormone medicine, can produce side effect such as health is got fat, resistance decline, blood sugar increasing, digestive tract ulcer, electrolyte disturbance.In addition, irregular application hormone medicine very easily makes the state of an illness increase the weight of repeatedly, increases the difficulty of seance rehabilitation.The calcitonin side effect is also a lot, like loss of appetite, face flushing, play measles, feel sick and giddy etc.What need special proposition is; Controversies in hormone replacement in the elderly is once as the first-selection of treating women's postmenopausal osteoporosis; But new research shows that life-time service estrogen possibly cause endometrium and cyclomastopathy, increases the danger that carcinoma of endometrium and breast carcinoma take place.
In recent years, the research of relevant Asterias amurensis Lutken active component and pharmacologically active receives concern both domestic and external day by day.Up to now, various countries' research worker has obtained tens types of chemical substances in succession in the Asterias amurensis Lutken body, comprising chemical constituents such as saponin, sterol, alkaloid, anthraquinone, polypeptide, aminoacid, polysaccharide, lipid, protein.Research shows, that starfish extract and compound preparation thereof have is anticancer, arrhythmia, bring high blood pressure down, promote multiple functions such as learning and memory, anti-bacteria and anti-virus, haemolysis, resisting fatigue.Asterias amurensis Lutken is usually used in treating diseases such as anxious chronic infantile convulsion, tetanus, epilepsy, gastric abscess, acid regurgitation, diarrhoea, gastric and duodenal ulcers, thyromegaly, otitis media.
Summary of the invention
The objective of the invention is to through research, and combine Chinese pharmaceutical therapeutics and galenic pharmacy, the application of exploitation Asterias amurensis Lutken in the medicine of preparation treatment osteoporosis the Asterias amurensis Lutken pharmacodynamics.
The present invention at first discloses the application of Asterias amurensis Lutken in the medicine of preparation treatment osteoporosis.Wherein said Asterias amurensis Lutken is Asteriidae animal asterias rollestoni (Asterias rollestoni bell), Asterias amurensis (Asteriasamurensis lutken) or Heliasteridae animal solaster dakisoni Verrill (Solaster dawsoni verrill).
Need to prove; The described Asterias amurensis Lutken of the invention described above is the Chinese crude drug title, and it both can be to cut into decoction pieces, supplied decoction; Or take or transfer the Chinese crude drug of deposited external after grinding, also can be to supply the pharmaceutical factory to produce the crude drug of Chinese traditional patent formulation preparation or pharmaceuticals industry extraction active chemical.Know like those skilled in the art, the title of Chinese crude drug is unique, but its source can be one or more, and the biological name in Chinese crude drug source maybe be identical or different with the Chinese crude drug title.The biogenetic derivation of Chinese crude drug Asterias amurensis Lutken described in the present invention is Asteriidae animal asterias rollestoni (Asterias rollestoni bell), Asterias amurensis (Asterias amurensislutken) or Heliasteridae animal solaster dakisoni Verrill (Solaster dawsoni verrill).
The medicine of the described application of the invention described above Asterias amurensis Lutken preparation treatment osteoporosis, need carry out processed as follows to the raw material Asterias amurensis Lutken:
1. the raw material Asterias amurensis Lutken of water content 2%~10% was steamed 2~4 hours with flowing steam;
2. dry after water content is lower than 7% for 60 ℃~80 ℃ and take out, 18~26 ℃ of temperature, relative humidity 45%~65% condition held is to room temperature;
3. pulverize, cross 100~300 mesh sieves;
4. preparation.
In the medicine of above-mentioned application Asterias amurensis Lutken preparation treatment osteoporosis, to the control preferred 3%~5% of raw material Asterias amurensis Lutken water content.Adopt flowing steam that the purpose that raw medicinal material steams is had two: the first reduces zest (or sensitization); It two can promote to absorb, and improves bioavailability.In order to take and to measure conveniently, preferably the Asterias amurensis Lutken powder after the above-mentioned processing is processed capsule or pill.
The above-mentioned Asterias amurensis Lutken application in the medicine of preparation treatment osteoporosis among the present invention, preferably with the oral forms administration, the Coming-of-Age Day taking dose dose 1~3g that makes a living takes at twice; 4~6 weeks of the course of treatment.
At present, still there is not the relevant report that the Asterias amurensis Lutken single medicinal material is used in the treatment medicine for treating osteoporosis.Research through us shows that Asterias amurensis Lutken has the increase Oesteoblast growth, promotes the bone calcific deposit, and effects such as bone density improving are remarkable for treatment osteoporosis effect.Adopt the medicine of the prepared treatment osteoporosis of technical scheme of the present invention, have in the clinical practice treatment well, the high characteristics such as without any side effects of instant effect, cure rate.And the medicine source is sufficient, and manufacture method is simple, and cost is low.
The specific embodiment
As do not have specified otherwise, this part content institute use equipment comprises:
DT3 type multi-function extractor: 110 ℃ of temperature, design pressure 0.09MPa in jar;
CT-C-II type heated-air circulation oven: 60 ℃~80 ℃;
LF3-600 type pulverizer.
Embodiment 1: be the capsule of feedstock production treatment osteoporosis with Asterias amurensis Lutken (asterias rollestoni)
1. get water content 3% asterias rollestoni 300g, steamed 2 hours with flowing steam;
2. dry and be lower than 7% back to water content and take out for 60 ℃, 20 ± 2 ℃ of room temperatures, relative humidity 45%~65% condition held is to room temperature;
3. pulverize, cross 100 mesh sieves;
4. incapsulate, process 1000 altogether.
The Asterias amurensis Lutken capsule of present embodiment be used as the treatment osteoporosis medicine, with the oral forms administration, Coming-of-Age Day taking dose be 4~10, take at twice; 4~6 weeks of the course of treatment.
Embodiment 2: be the pill of feedstock production treatment osteoporosis with Asterias amurensis Lutken (solaster dakisoni Verrill)
1. get water content 6% solaster dakisoni Verrill 30g, steamed 3 hours with flowing steam;
2. dry and be lower than 7% back to water content and take out for 70 ℃, 22 ± 2 ℃ of room temperatures, relative humidity 45%~65% condition held is to room temperature;
3. pulverize, cross 140 mesh sieves;
4. add an amount of water pill with the 25g refined honey, drying is processed 500 water-honeyed pills.
The Asterias amurensis Lutken water-honeyed pill of present embodiment be used as the treatment osteoporosis medicine, with the oral forms administration, Coming-of-Age Day taking dose be 20~50 balls, take at twice; 4~6 weeks of the course of treatment.
Embodiment 3: be the pill of feedstock production treatment osteoporosis with Asterias amurensis Lutken (Asterias amurensis)
1. get water content 8% Asterias amurensis 30g, steamed 4 hours with flowing steam;
2. dry and be lower than 7% back to water content and take out for 80 ℃, 24 ± 2 ℃ of room temperatures, relative humidity 45%~65% condition held is to room temperature;
3. pulverize, cross 180 mesh sieves;
4. add an amount of water pill with the 25g refined honey, drying is processed 500 water-honeyed pills.
The Asterias amurensis Lutken water-honeyed pill of present embodiment be used as the treatment osteoporosis medicine, with the oral forms administration, Coming-of-Age Day taking dose be 20~50 balls, take at twice; 4~6 weeks of the course of treatment.
Embodiment 4: Asterias amurensis Lutken causes the therapeutical effect research of rats with osteoporosis to retinoic acid
Laboratory animal: SD rat, body weight 170~230g, male and female half and half; Raise 24 ℃~28 ℃ of room temperatures, relative humidity is 40%~60%, and the clean rank of animal feeding room is 100,000 grades.
The Asterias amurensis Lutken powder that experiment medicine: embodiment 1 is prepared faces with preceding and is made into suspension with distilled water; The preparation principle is to guarantee during the multiple dose group administration of present embodiment is tested that the filling body of stomach of several dose groups is long-pending approaching.
Positive control drug: ethoxy Alendronate
Rat is divided into 6 groups at random, is respectively: normal control group, model control group, the basic, normal, high dose groups of Asterias amurensis Lutken and positive drug control group; Except that the normal control group, each is organized rat and all irritates clothes 7% (g/ml) retinoic acid solution, every day 1 time, continuous 14 days by the dosage of 70mg/kg body weight.After the end, the basic, normal, high dose groups of Asterias amurensis Lutken is pressed the dosed administration of 0.8g/kg, 1.6g/kg, 2.4g/kg respectively; Positive drug ethoxy Alendronate is pressed 0.05g/kg body weight dosed administration; Normal control group and model group are irritated clothes equal-volume distilled water, and every day, gastric infusion was 1 time, and continuous 28 days, claim body weight weekly one time, next all dosage is confirmed in adjustment according to body weight.
Observation index: put to death animal in 2 hours after the last administration, get rat bilateral femur, peel meat and other tissue off, wherein a side femur is done rat femur scanning on dual intensity X line borne densitometers, measures bone density (g/cm 2), claim femur heavy (W), survey bone long (L), bone diameter (D) calculates bone lines of expression density (W/L), apparent surface density (W/Ld).The opposite side femoral head is fixing in 10% neutral formalin liquid, and paraffin section is made in conventional decalcification after the decalcification, HE dyeing, and microscopically is surveyed the bone trabecula width.
The result is shown in table 1~3:
Table 1 Asterias amurensis Lutken causes the influence of osteoporosis rat femoral bmd to retinoic acid
Group Dosage (g/kg) Number of animals (only) Femoral bmd (g/cm 2)
The normal control group - 10 0.178±0.007
Model control group - 9 0.151±0.008 △△
The Asterias amurensis Lutken low dose group 0.8 10 0.157±0.014
Dose groups in the Asterias amurensis Lutken 1.6 10 0.171±0.006 **
The Asterias amurensis Lutken high dose group 2.4 10 0.179±0.011 **
Positive controls 0.05 10 0.174±0.011 **
Compare with model control group *<0.01
Compare with the normal control group △ △P<0.01
The result shows: middle and high dosage Asterias amurensis Lutken can significantly improve the rat femur bone density.
Table 2 Asterias amurensis Lutken causes the exponential influence of osteoporosis rat bone to retinoic acid
Group Dosage (g/kg) Number of animals (only) The heavy W (g) of femur bone Femur length L (cm) Femur diameter D (cm) Femur apparent density W/L (g/cm) The apparent surface density W/Ld (g/cm of femur 2)
The normal control group - 10 0.691± 0.007 3.344± 0.013 0.361± 0.021 0.213± 0.009 0.576± 0.02
Model control group - 9 0.535± 0.015 △△ 3.107± 0.006 0.348± 0.008 0.168± 0.011 △△ 0.489± 0.017
The Asterias amurensis Lutken low dose group 0.8 10 0.551± 0.014 3.117± 0.101 0.347± 0.01 0.175± 0.011 0.510± 0.022
Dose groups in the Asterias amurensis Lutken 1.6 10 0.556± 0.004 3.121± 0.055 0.349± 0.018 0.188± 0.008 * 0.505± 0.03
The Asterias amurensis Lutken high dose group 2.4 10 0.616± 0.011 ** 3.252± 0.17 * 0.352± 0.02 0.193± 0.013 ** 0.541± 0.025 **
Positive controls 0.05 10 0.634± 0.008 ** 3.259± 0.098 * 0.354± 0.018 0.195± 0.012 ** 0.551± 0.017 **
Compare with model control group *P<0.05, *<0.01;
Compare with the normal control group P<0.05, △ △P<0.01.
The result shows: compare with the normal control group; Femur bone weight, length, apparent density and the apparent surface density of model control group rat all obviously descends; With respect to model group, femur bone weight, length, apparent density and the apparent surface density of Asterias amurensis Lutken high dose group and positive controls rat have all obviously improved.
Table 3 Asterias amurensis Lutken causes the influence of osteoporosis rat bone trabecula width to retinoic acid
Group Dosage (g/kg) Number of animals (only) Thigh little beam width (μ m)
The normal control group - 10 60.1±2.4
Model control group - 9 41.8±5.5 △△
The Asterias amurensis Lutken low dose group 0.8 10 43.1±9.5
Dose groups in the Asterias amurensis Lutken 1.6 10 47.6±3.3 *
The Asterias amurensis Lutken high dose group 2.4 10 50.4±8.8 *
Positive controls 0.05 10 55.5±3.5 **
Compare with model control group *P<0.05, *P<0.01;
Compare with the normal control group △ △P<0.01.
The result shows: compare with the normal control group, the little beam width of thigh of model control group rat obviously reduces; After giving the Asterias amurensis Lutken treatment, compare with the model matched group, the little beam width of the middle and high dose groups rat bone of Asterias amurensis Lutken all has improvement in various degree.

Claims (3)

1. the application of Asterias amurensis Lutken in the medicine of preparation treatment osteoporosis is characterized in that it being that Asterias amurensis Lutken processes through following step:
1. the raw material Asterias amurensis Lutken of water content 2%~10% was steamed 2~4 hours with flowing steam;
2. dry after water content is lower than 7% for 60 ℃~80 ℃ and take out, 18~26 ℃ of temperature, relative humidity 45%~65% condition held is to room temperature;
3. pulverize, cross 100~300 mesh sieves;
4. preparation;
Wherein said Asterias amurensis Lutken is Asteriidae animal asterias rollestoni, Asterias amurensis or Heliasteridae animal solaster dakisoni Verrill.
2. the application of Asterias amurensis Lutken according to claim 1 in the medicine of preparation treatment osteoporosis, the medicine that it is characterized in that described treatment osteoporosis be with the oral forms administration, and the Coming-of-Age Day taking dose dose 1~3g that makes a living takes at twice; 4~6 weeks of the course of treatment.
3. the application of Asterias amurensis Lutken according to claim 1 in the medicine of preparation treatment osteoporosis is characterized in that described preparation is capsule or pill.
CN2010101550922A 2010-04-23 2010-04-23 Application of starfishes to preparation of medicament for treating osteoporosis Active CN101804075B (en)

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CN102718832A (en) * 2012-03-05 2012-10-10 蒋鹏 Marine organism collagen peptide
TW201517931A (en) * 2013-11-15 2015-05-16 Tci Co Ltd A method for extracting substance from starfish
CN113564219B (en) * 2021-09-26 2021-12-24 渤海水产股份有限公司 Separation and purification method of active starfish peptide, active starfish peptide and application

Citations (1)

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Publication number Priority date Publication date Assignee Title
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Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
CN101347507A (en) * 2008-09-08 2009-01-21 大连美罗中药厂有限公司 Medicament composition for treating traumatology disease and preparation, use, medicinal preparation and quality control method thereof

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