CN103251650A - Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion - Google Patents

Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion Download PDF

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Publication number
CN103251650A
CN103251650A CN2013101850386A CN201310185038A CN103251650A CN 103251650 A CN103251650 A CN 103251650A CN 2013101850386 A CN2013101850386 A CN 2013101850386A CN 201310185038 A CN201310185038 A CN 201310185038A CN 103251650 A CN103251650 A CN 103251650A
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precancerous lesion
treasured
river deer
mucosa
purposes
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CN2013101850386A
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CN103251650B (en
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郑亮
陈寒昱
王媛媛
梅雨玫
李镇
赵太媛
冯进
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郑亮
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Abstract

The invention discloses an application of roe milk in preparation of a medicine used for preventing and treating gastric cancer and precancerous lesions. Roe milk is a milk block taken out form a glandular stomach of a young roe in a lactation period, has sweet taste and natural nature, has the effects of strengthening the spleen and stomach, helping digestion and removing stagnancy as well as building body and prolonging life and can be used for preparing a medicine composition and preparation used for improving the immunity and preventing and treating the gastric cancer and the precancerous lesions.

Description

The purposes of river deer treasured in the medicine of preparation prevention and treatment gastric cancer and cercinoma prophase pathologic change thereof
Technical field
The present invention relates to the application of a kind of medicinal active ingredient in the preparation medicine, relate in particular to the application of river deer treasured in the preparation medicine, belong to medical technical field.
Background technology
The river deer treasured belongs to famous and precious rare medical material, is the infantile dyspepsia piece that takes out the children river deer glandular stomach from age of sucking.According to Compendium of Material Medica record, the river deer treasured is warm in nature, and sweet in the mouth is flat, the effect that invigorating the spleen and regulating the stomach, dyspepsia and intestinal stasis relieving are arranged, braces up energy and delay senility.
Analyze after testing, the protein content of river deer treasured reaches 39%, contains 17 seed amino acids such as taurine and threonine simultaneously, and wherein 7 kinds is the human body essential amino acid, and content is higher than general milk product, and wherein the content with glutamic acid, proline, valine and lysine is high especially; The result of inorganic elements analysis shows that the calcareous content of river deer treasured is higher, and per 100 gram dry powder contain 959.5mg, and the content of copper, manganese is the several times of other food, and content and the milk product of zinc, magnesium are suitable, and the river deer treasured contains the immunoglobulin amount up to 28.5%.
By to experiment mice studies have shown that the river deer treasured can improve the pepsic vigor of mice, and can improve mice with spleen deficiency serum gastrin content very significantly.Mensuration to the mouse small intestine propulsion functions shows that the river deer treasured can obviously promote small intestinal peristalsis.The tradition of river deer treasured is applied as facilitating digestion function and treatment indigestion.
Gastric cancer is one of common malignancy, and its sickness rate and mortality rate all occupy the prostatitis of malignant tumor in China.The canceration of gastric epithelial cell is a progressive process, and in the normal experience lasting preventing precancerous lesion of stomach cancer stage for many years, some patient finally can be developed into gastric cancer.Therefore prevent or the treatment gastric precancerous lesion, stoping precancerous lesion to be converted into pernicious gastric cancer is an important channel that prevents and treats gastric cancer, and China's cancer morbidity and patient death rate are significant for reducing.The inventor is through research with keen determination, especially for river deer treasured discovering in the therapeutical effect of gastric precancerous lesion and treatment mechanism, the river deer treasured can be prevented and treated the generation of gastric precancerous lesion and then prevention gastric cancer well, widened the application of river deer treasured, also prevention and the treatment for gastric cancer provides new therapeutic scheme.
Summary of the invention
According to a first aspect of the present invention, provide the river deer treasured for the preparation of the prevention or the treatment gastric precancerous lesion medicine in purposes.
According to another aspect of the present invention, the pharmaceutical composition that contains the river deer treasured is provided, make with one or more pharmaceutically acceptable carriers or excipient by the active component river deer is precious.
River deer treasured of the present invention can adopt method well known in the art to obtain, and for example raises and train the newborn river deer that breeds more than the three generations and is sucking formation Off-white solid or semi-solid block in river deer milk back stomach, especially abomasum (glandular stomach) meeting, and underwent operative is drying to obtain after taking out.
The present invention the concrete river deer treasured that adopts be the commercially available prod.
The river deer treasured can be used as first activating agent in the pharmaceutical composition of the present invention, can also contain second activating agent in the pharmaceutical composition, and second activating agent is selected from Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Poria, Semen Coicis, Vascular aurantii, Radix Ginseng, the Radix Astragali, Cordyceps mycelium.
The amount of the contained river deer treasured in minimum dose unit of pharmaceutical composition of the present invention is 30mg.
Product of the present invention comprises and contains medicine and the health product that relating to of river deer treasured prevents and/or treats the gastric mucosa precancerous lesion, prevents and treats the gastric cancer related application.
The invention still further relates to pharmaceutical composition and the pharmaceutical applications of the precancerous lesion that prevents and/or treats other mucosa such as bladder, cervix uteri, uterus, small intestinal or large intestine, oral cavity, nasopharynx, esophagus etc.
Pharmaceutical composition of the present invention can be made and be suitable for any dosage form that the human or animal uses.Route of administration can be intestinal or parenteral route, as: oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum etc.Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (comprising true solution and colloid solution), Emulsion, microemulsion, suspensoid, injection (comprising aqueous injection, injectable powder and transfusion), eye drop, nasal drop, lotion, liniment etc.; Solid preparation can be tablet (comprising ordinary tablet, enteric coatel tablets, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, oral cavity disintegration tablet etc.), capsule (comprising hard capsule, soft capsule, enteric coated capsule), granule, powder, micropill, drop pill, suppository, membrane, paster, the agent of gas (powder) mist, spray etc.; Semi-solid preparation can be ointment, gel, paste etc.Preparation can be made ordinary preparation, also can be slow releasing agent, controlled release agent, targeting preparation and various particulate delivery system.
Dosage form of the present invention can be used usual any method production of using in pharmaceutical preparation technology, is not particularly limited.
The inventor adopts chemical carcinogen to induce gastric mucosa of rat hyperplasia of prostate/precancerous lesion/stomach malignant cancer model, studied the effect that precious generation evolution, prevention gastric precancerous lesion and the pernicious gastric cancer that suppresses gastric mucosa of rat hyperplasia of prostate → gastric mucosa precancerous lesion → stomach malignancy that chemical carcinogen two leads of river deer takes place, proof river deer treasured can obviously suppress the intestinal epithelial metaplasia of gastric mucosa, alleviate the precancerous lesions such as atypical hyperplasia of stomach basal cell, reduce the gastric tumor growth, reduce generation rate of malignant tumour.Proved that the river deer treasured has the control gastric precancerous lesion, the effect of the pernicious carcinogenesis of prevention stomach.
The present invention proves that through rat test the river deer treasured can improve the rat body weight that chemical carcinogen is induced, and suppresses the Gastric Mucosal Cells hypertrophy, reduces the incidence rate of gastric mucosa precancerous lesion atypical hyperplasia, intestinal epithelial metaplasia, reduces the stomach malignancy incidence rate.
The specific embodiment
The present invention is described in further detail below in conjunction with specific embodiment.
Embodiment 1: the preparation of the precious aqueous solution of river deer
Effective ingredient river deer treasured among the present invention can adopt method well known in the art to obtain, for example raise and train the above newborn river deer of breeding three generations and sucking river deer milk back stomach, especially form Off-white solid or semi-solid block in abomasum (glandular stomach) meeting, underwent operative is drying to obtain after taking out.
1. select the above newborn river deer of breeding three generations of raising and train of 12 ages in days to raise with river deer breast bottlefeeding.After three hours, lump can be touched in this breast river deer glandular stomach position;
2. newborn river deer is anaesthetized sterilization, bring aseptic operating room into, be fixed in operating-table, carry out the live body operation, cut glandular stomach open, take out Off-white solid or semi-solid block, 200 mesh sieves are crossed in dry, pulverizing, namely obtain can be used in the river deer treasured that the present invention uses.
3. the precious aqueous solution dosage of river deer: rat dose,equivalent=people one daily dose * 0.018*5 (70 kilograms of calculating of people's standard body weight), 0.5 times of dose,equivalent as low dose of, and dose,equivalent is middle dosage, and twice be heavy dose.The precious aqueous solution of river deer is heated to during use about 15 ℃ and uses to preserve in 4 ℃ of refrigerators.
Effective ingredient river deer treasured among the present invention also can the commercially available prod, and the used river deer treasured of following experimental example is the commercially available prod.
Experimental example
Grouping: 42 of cleaning level Wistar male rats, body weight is between 180g-220g.Fed 7 days at the laboratory adaptability, room temperature control is between 18-25 ℃, show behind the normal growth that fasting can't help water and weighed in 12 hours again, with randomized and district's group method of dividision into groups at random, rat is divided into 8 of blank groups, 34 of model group, adopt MNNG solution freely to drink to model group and close the irregular diet modeling, from 2 rats of model group picked at random, cut open the belly and get the situation that stomach is observed gastric mucosa, after confirming the modeling success, 32 rats are divided into model control group, the precious small dose group of river deer, middle dosage group, heavy dose of group, every group each 8 at random.
The modeling of gastric precancerous lesion (PLGC) rat: adopting with MNNG is principal element, the modeling method modeling of associating additive method.Adopt the free drinking technique of MNNG to cooperate and press down acid, irregular diet and NaTDC, ethanol administration by gavage associating modeling.Earlier MNNG is formulated as the storage liquid of 1g/L concentration with distilled water, weekly configuration once, lucifuge, stored refrigerated are packed into and are posted the drinking-water bottle of black lucifuge paper, freely drink for rat.Except blank group rat, all the other respectively organize the ranitidine hydrochloride that adds in the rat word material with 0.03%, give hungry full alternate nursing, took food 2 days, and fasting 1 day, irritate stomach with 20mmol/L deoxycholic acid sodium solution with dosage 10mL/kg that afternoon of taking food after 2 days; 1 day that afternoon of fasting, irritate stomach with 40% ethanol 10mL/kg, continued for 16 weeks.Blank group gives the equivalent normal saline and irritates stomach, common standard word material.The 16th weekend of modeling, from the model group rat, randomly draw 2 rats, get gastric antrum and body of stomach tissue each after one, dye with conventional haematoxylin one Yihong, after 20% formalin fixed, the gastric mucosa of observing 2 rats under the light microscopic all has atrophy, and intestinalization and atypical hyperplasia variation occur, to confirm successful duplicating model.
Administration: the precious aqueous solution of 16 week of modeling back river deer is irritated stomach with 25mg/kg, 50mg/kg, 100mg/kg dosage, and every day 1 time, blank group, model control group give the 10ml/kg normal saline and irritate stomach, and every day 1 time, treatment group administration time was for 12 weeks.
The HE stained preparation is gathered: after putting to death rat, cut open the belly and get stomach, take out full stomach from breaking apart from cardia and pylorus 1.5cm, cut full stomach open in the greater gastric curvature side, get 0.2 * 2.0cm strip gastric tissue, place 4% paraformaldehyde solution fixedly behind the 24h rapidly, paraffin embedding, be equipped with HE dyeing, observe the variation of gastric mucosa under the light microscopic.
Experimental result
1, ordinary circumstance and body weight
Blank group rat expression is freely, energy is good, and happiness is moving flexibly, fur gloss, and diet is normal; Model control group rat lethargy, tired in moving the in disorder gloss of owing of fur, diet reduces, and medication group rat all has in various degree activity and diet to increase, and body weight increases, fur is owed gloss, and blank is organized the rat expression to general state, energy is not good enough, and other performances are better than model control group.
Table 1: experimental rat body weight at 12 weekend changes situation
Group N (only) Body weight (g)
Blank group 8 204.65±10.05
Model control group 8 176.65±6.08*
The precious low dose group of river deer 8 194.95±11.56**
Dosage group in the river deer treasured 8 199.26±10.04***
The precious high dose group of river deer 8 198.54±11.71**
Annotate: compare * P<0.01 with the blank group, compare * * P<0.05 with model control group, * * * P<0.01.
2, gastric mucosa pathology
(1) perusal
Model group rat coat of the stomach is thinner, and elasticity is relatively poor, owes gloss, no mucus, and mucosa is pale asphyxia or canescence, and part mucosa outward appearance is dispersed in the petechia and the fine grained sample changes; Blank group rat coat of the stomach elasticity is good, glossy, and mucous membrane surface is smooth smooth, and lining mucus is more, the mucosa pinkiness; The basic, normal, high dosage group of Chinese medicine coat of the stomach elasticity is better, and mucosa is light red or kermesinus, and pleat is darker relatively, and visible a small amount of mucus is adhered to.
(2) HE dyeing microscopic examination
Blank group: gastric epithelial is complete, and the body of gland marshalling is tight in the cellular morphology homogeneous, lamina propria, a spot of lymphocyte that sporadically appears, and tangible cell infiltration is not seen by body of stomach and gastric antrum portion.
Model control group: gastric mucosa part body of gland atresia, the part body of gland occurs back-to-back or is total to the wall phenomenon, and gastric pits prolongs, and visible inflammatory cell soaks in the lamina propria, infiltration can reach muscularis mucosae deeply, the visible lymphocyte of part mucosa is assembled and lymph follicle forms, blood vessel hyperplasia, and gastric antrum portion body of gland arrangement disorder hypertrophy is obvious, basilar part body of gland epithelial proliferation, as seen goblet cell, nuclear hyperchromatism even double-core have the atypical hypertrophy of moderate and intestinal epithelial metaplasia.
The precious low dose group of river deer: the gastric mucosa body of gland is arranged more neat relatively, and cellular morphology is than homogeneous, and the boundary of Glandular Epithelium and Gland pipe is clear, the visible atrophy of part body of gland, intestinalization, and cell infiltration mainly is confined to the mucosa shallow-layer, and intrinsic body of gland is kept perfectly.
Dosage group in the river deer treasured: body of stomach, gastric antrum portion mucosal inflammation than model group, the river deer treasured is low, high dose group is light, visible edema, hyperemia and the epithelium non-viable non-apoptotic cell comes off, lymphocyte and cell infiltration, the visible a small amount of eosinophilic granulocyte of part and neutrophil infiltration under the mirror.
The precious high dose group of river deer: the rat stomach mucosal epithelium is complete than model group, and cellular morphology is homogeneous relatively, and the interior body of gland of lamina propria is arranged closeer, a spot of lymphocyte that sporadically appears, and the boundary of Glandular Epithelium and Gland pipe is clear, and cell infiltration mainly is confined to the mucosa shallow-layer.
(3) statistics
The precious low dose group of river deer is light than model group mucosa pathological changes, and atrophic focus scope is little, degree is light, 4 routine glandular epithelium dysplasias (hypertrophy be gently, moderate 2 examples, in, severe 2 examples), 5 routine intestinal epithelial metaplasias.The dosage group is light than model group mucosa pathological changes in the river deer treasured, and atrophic focus scope is little, degree is light, 4 routine glandular epithelium dysplasias (hypertrophy is light, moderate 3 examples, in, severe 1 example), 4 routine intestinal epithelial metaplasias.During high dose group mucosa dysplasia and intestinal epithelial metaplasia improve, low dose group is obvious, 3 still have dysplasia (1 moderate, 2 light, moderates), 4 intestinal epithelial metaplasias.Blank group is not seen dysplasia and intestinal epithelial metaplasia and gastric mucosa atrophy pathological changes.Model group mucosa pathological changes is not seen recovery, and the trend of increasing the weight of is arranged, and shows as atrophy kitchen range scope and strengthens, and the dysplasia degree increases the weight of (3 of its mild or moderates, 4 of moderates, 1 of severe), and intestinal epithelial metaplasia example number increases to 5.
Table 2: experimental rat gastric mucosa at 12 weekend changes situation
Group N Atrophic gastritis Dysplasia Intestinal epithelial metaplasia
Blank group 8 0 0 0
Model control group 8 8 8 5
The precious low dose group of river deer 8 8 4 5
Dosage group in the river deer treasured 8 8 4 4
The precious high dose group of river deer 8 7 3 4
The result shows: the precious aqueous solution of river deer has the gastric precancerous lesion of improvement rat ordinary circumstance, improves body weight, the effect of prevention and treatment gastric precancerous lesion, the pernicious gastric cancer incidence rate of minimizing.

Claims (6)

1. the river deer treasured is for the preparation of the purposes in the pharmaceutical composition that prevents and/or treats the mucosa precancerous lesion.
2. purposes as claimed in claim 1, wherein the mucosa precancerous lesion is gastric precancerous lesion.
3. purposes as claimed in claim 2, wherein the mucosa precancerous lesion is the precancerous lesion that is selected from following mucosa: bladder, cervix uteri, uterus, small intestinal, large intestine, oral cavity, nasopharynx or esophagus.
4. as each described purposes among the claim 1-3, wherein the river deer treasured also contains pharmaceutically acceptable carrier or excipient as unique active component in the pharmaceutical composition.
5. purposes as claimed in claim 4, wherein the river deer treasured also contains second activating agent as first activating agent in the described pharmaceutical composition, and second activating agent is selected from Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Poria, Semen Coicis, Vascular aurantii, Radix Ginseng, the Radix Astragali, Cordyceps mycelium.
6. purposes as claimed in claim 4, wherein pharmaceutical composition is prepared to and is suitable for the human or animal and uses dosage form, and described dosage form is selected from solution, Emulsion, suspensoid, injection, tablet, capsule, granule, powder, micropill, drop pill etc.
CN201310185038.6A 2013-05-20 2013-05-20 Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion Expired - Fee Related CN103251650B (en)

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Cited By (1)

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CN105125606A (en) * 2015-07-17 2015-12-09 浙江大学 Chewable tablet for improving immunity and preparation method of chewable tablet

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Publication number Priority date Publication date Assignee Title
CN105125606A (en) * 2015-07-17 2015-12-09 浙江大学 Chewable tablet for improving immunity and preparation method of chewable tablet
CN105125606B (en) * 2015-07-17 2018-10-19 浙江大学 Improve the chewable tablets and preparation method thereof of immunity

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