CN1663608A - Medicine for treating infantile anorexia - Google Patents

Medicine for treating infantile anorexia Download PDF

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CN1663608A
CN1663608A CN 200410104433 CN200410104433A CN1663608A CN 1663608 A CN1663608 A CN 1663608A CN 200410104433 CN200410104433 CN 200410104433 CN 200410104433 A CN200410104433 A CN 200410104433A CN 1663608 A CN1663608 A CN 1663608A
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medicine
chinese medicine
rhizoma
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fructus
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CN100360179C (en
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赵恒�
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XI'AN HENGTONG GUANGHUE PHARMACEUTICAL CO Ltd
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Abstract

The present invention is a medicine for treating infantile anorexia, especially is a medicine prepared by mixing biological preparation and Chinese traditional medicine for treating infantile anorexia. Its component mainly includes Alpha-mannan peptides 10-40%, and invigorating vital energy strengthening the spleen Chinese traditional medicine 60-90%. Its component also includes Alpha-mannan peptides 10-40%, invigorating vital energy strengthening the spleen Chinese traditional medicine 30-60%, and regulating vital energy strengthening the spleen resolving dampness Chinese traditional medicine 10-40%. Its component also includes Alpha-mannan peptides 10-40%, invigorating vital energy strengthening the spleen Chinese traditional medicine 10-40%, regulating vital energy strengthening the spleen resolving dampness Chinese traditional medicine 10-30%, and promoting blood and qi circulation Chinese traditional medicine 10-40%. The medicine for treating infantile anorexia is a Chinese Western composite preparation, combines the current medicine with traditional medicine scientifically, exerts their cooperating function, and has full comprehensive curative effect for infantile anorexia, and has no toxic and side effects.

Description

A kind of medicine for the treatment of infantile anorexia
Affiliated technical field
The invention belongs to a kind of medicine for the treatment of infantile anorexia, particularly about a kind of medicine of the treatment infantile anorexia that is mixed and made into biological preparation and Chinese medicine.
Background technology
Infantile anorexia is commonly encountered diseases, the frequently-occurring disease of department of pediatrics, and with not desire feed for a long time, very then refusing to eat is a clinical characters.It not only influences children's upgrowth and development, and is healthy, also is easy to concurrent other diseases.Apositia is the unbalanced a kind of performance of child's digestive functional disturbance, digestive function, causes serious malnutrition with extremely weak.More common in the urban children, be more common in 1～6 years old child.The child who has suffered from apositia, the gastrointestinal smooth muscle hypotonia, digestive juice secretion reduces, and the activity of various digestive enzyme also descends, and the central nervous system is to the adjusting disequilibrium of digestive function simultaneously.
At present, infantile anorexia is subjected to the extensive concern of society and medical circle day by day, to the also rising day by day of demand of its medicine.Modern medicine adopts zinc agent treatment more, but the zinc agent can only improve symptom, can not solve root problem, and some untoward reaction appear in life-time service zinc agent meeting, and simple zinc supplement also can influence the absorption of copper, calcium, ferrum, causes each trace element imbalance of internal body.In recent years, domestic medicine about infantile anorexia has many researchs, but lacks effective Western medicine clinically at present, also lacks the active drug at the incoordination between the spleen and stomach that occupies the majority in the infantile anorexia, dysfunction of the spleen in transportation card infant in the Chinese patent medicine.This works out the pharmaceutical preparation of highly effective and safe with regard to an urgent demand medicine worker.
Summary of the invention
] purpose of the present invention is exactly to make a kind of medicine for the treatment of infantile anorexia, this medicine adopts the medicine of the treatment infantile anorexia that biological preparation and Chinese medicine is mixed and made into.It brings into play both synergism with modern medicine and traditional medicine science, combine cleverly, comprehensive comprehensive curative effect is played in the treatment of infantile anorexia, and have no side effect taking convenience.
Technical scheme of the present invention is: design a kind of medicine for the treatment of infantile anorexia, it is characterized in that: its composition mainly comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 60-90%.
Its composition also comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 30-60%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-40%.
Its composition also comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 10-40%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-40%.
Its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%.
Its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%, vitamin (B1, B2, B6) 2-5%.
Its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%, vitamin (B1, B2, B6) 2-5%, zinc sulfate 5-10%.
Described air making-up and spleen enlivening class Chinese medicine has: Radix Glycyrrhizae, the Rhizoma Atractylodis Macrocephalae, Radix Codonopsis, the Radix Astragali, Radix Ginseng, Rhizoma Dioscoreae, Fructus Jujubae, Poria; Regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine has: Poria, the Rhizoma Atractylodis Macrocephalae, Polyporus, Rhizoma Alismatis, the Radix Aucklandiae, Fructus Amomi, Folium Perillae, Pericarpium Arecae, Cortex Mori, Fructus Chaenomelis; Blood-activating and qi-promoting class Chinese medicine has: Semen Persicae, Flos Carthami, rhizoma sparganic, Rhizoma Curcumae, Herba Lycopi, Lignum Sappan, Herba Artemisiae Anomalae, Herba Leonuri, cattle lacquer, Hirudo, Tabanus, Olibanum, Myrrha; Promoting digestion and removing stagnation class Chinese medicine has: crataegus pin natifida var. Major, Fructus Hordei Germinatus, Fructus Setariae Germinatus, Massa Medicata Fermentata, Endothelium Corneum Gigeriae Galli, Herba Pogostemonis, Rhizoma Alpiniae Officinarum, Semen Alpiniae Katsumadai, Fructus Amomi, Semen Myristicae, the Radix Aucklandiae, Rhizoma Zingiberis Recens, Fructus Schisandrae Chinensis.
Described medicament per 1000 contains α-mannatide 300g, Radix Glycyrrhizae 150g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 100g, Radix Ginseng 50g, Rhizoma Dioscoreae 100g, Fructus Jujubae 100g, Poria 100g.
The every 1000g of described medicament contains α-mannatide 300g, Radix Glycyrrhizae 50g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 50g, Radix Ginseng 45g, Rhizoma Dioscoreae 50g, Fructus Jujubae 50g.Poria 30g, Rhizoma Atractylodis Macrocephalae 35g, Polyporus 30g, Rhizoma Alismatis 30g, Radix Aucklandiae 35g, Fructus Amomi 30g, Folium Perillae 55g, Pericarpium Arecae 50g, Cortex Mori 30g, Fructus Chaenomelis 30g.
Described medicament per 1000 contains α-mannatide 200g, Radix Glycyrrhizae 50g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 25g, Radix Astragali 25g, Radix Ginseng 25g, Rhizoma Dioscoreae 50g, Fructus Jujubae 50g, Poria 25g, Rhizoma Atractylodis Macrocephalae 15g, Polyporus 15g, Rhizoma Alismatis 20g, Radix Aucklandiae 25g, Fructus Amomi 20g, Folium Perillae 45g, Pericarpium Arecae 30g, Cortex Mori 30g, Fructus Chaenomelis 30g, Semen Persicae 20g, Flos Carthami 20g, rhizoma sparganic 20g, Rhizoma Curcumae 20g, Herba Lycopi 20g, Lignum Sappan 20g, Herba Artemisiae Anomalae 20g, Herba Leonuri 25g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 25g, Myrrha 20g.
The every 1000g of described medicament contains α-mannatide 200g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g.
The every 1000g of described medicament contains α-mannatide 150g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g, vitamin (B1, B2, B6) 50g.
The every 1000g of described medicament contains α-mannatide 130g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g, vitamin (B1, B2, B6) 20g, zinc sulfate 50g.
Characteristics of the present invention are: the pathogeny of relevant infantile anorexia, traditional traditional Chinese medical science is thought: The spleen and stomach provide the material basis of the acquired, source of generating QI and blood.Children's's internal organs are tender and lovely, and essence derived from food does not fill, and the spleen tending to insufficiency usually adds the influence of improper diet, sickness influence and feelings will, easily causes dysfunction of the spleen in transportation, dysfunction of spleen and stomach, and fortuneization mistake department, it is impaired that taste are received the function of becoming thoroughly decomposed, and change paddy incapability causes anorexia.Infantile anorexia belongs to the category of infantile malnutrition, the infantile malnutrition life in taste, weakness of the spleen and stomach, all kinds of diseases and ailments are given birth to, children's's prolonged illness, tonifying the spleen and stomach and healthy energy, then sick spontaneous recovery.Modern medicine is thought: appetite is that body need supplement the nutrients and a kind of physiological natural reaction of heat, it is one of higher nervous activity phenomenon, be positioned at the feeding center of hypothalamus and satiety center by the Physics OF Nerve Impnlse of accepting to pass on through cerebral cortex and limbic system from vagus nerve, visceral nerve to appetite generation regulating action, disease and Nervous and Mental Factors can make cerebral cortex and hypothalamus suppress, digestive juice secretion is reduced, and the stomach muscular tension reduces and causes anorexia.Modern study also shows, anorexia also causes nutrient such as zinc, vitamin B group to lack in close relations with monophagia.Vitamin B group lacks and to cause that anorexia knows for everybody.Zinc is to keep the necessary trace element of human body normal activities, and its function mainly is the synthetic and metabolism that participates in plurality of enzymes in the human body.If the human body zinc deficiency promptly can influence people's the sense of taste, reduce appetite, thereby infantile anorexia occurs.Long-term anorexia will cause the human body energy resource supply not good, influences people's body rate of metabolism, and the growth promoter of body is hindered, thereby reduces resistance and the immunity of human body to various diseases.Infantile anorexia and nutrient shortage, hypoimmunity and weak and sicklyly often follow mutually influence each other reciprocal causation.Therefore, the treatment of infantile anorexia is very important.Common cause and pathogeny according to infantile anorexia; the present invention is principle with the combination of Chinese and Western medicine; the traditional Chinese medical science is with invigorating the spleen and stomach and promoting digestion and removing stagnation and execute in the side; Radix Codonopsis, Rhizoma Atractylodis Macrocephalae air making-up and spleen enlivening, Pericarpium Citri Reticulatae, the removing dampness of Cortex Magnoliae Officinalis regulating qi-flowing for strengthening spleen, Rhizoma Chuanxiong blood-activating and qi-promoting; Fructus Oryzae Germinatus, Fructus Setariae Germinatus promoting digestion and removing stagnation; doctor trained in Western medicine is replenished and closely-related zinc element of anorexia and vitamin B group, and α-mannatide has immunological enhancement, can protect gastrointestinal function.Such prescription is formed the ability that had both increased transporting and transforming function of the spleen and stomach, digested and assimilated, and replenishes the material base of keeping good appetite again, improves local and general immunity function, strengthen the absorption of small intestinal to nutrition, the combination of Chinese and Western medicine is complemented each other, to reach the purpose of " logical canal water filling, moist non-irrigated Seedling ".Advantage of the present invention is embodied in can improve the gastrointestinal tract local function, can regulate whole body functions such as immunity, nerve, endocrine again.
The specific embodiment
Because the present invention is carried recoverable space craft (spacecraft or retrievable satellite) with the Alpha-hemolytic streptococcus strain, utilize the comprehensive function of factors such as little in the space (zero) gravity, cosmic ray, alternating magnetic field, fine vacuum, hyperpyrexia deep cooling, make the dna double chain structure fracture of bacterial strain, genome is reset, thereby produces new bacterial strain.After returning ground, bacterial strain through space treatment is cultivated and screened, by studying contents such as its morphological characteristic, cultural characteristic, biochemical reactions, metabolite, hereditary character and protein expression, hereditary stability, pilot scale production target, optimize the stable strain of plus variant, inherited character wherein, the medicine of the ulcerative colitis that after cultivation and fermentation, obtains medical treatment.This strain in China Committee for Culture Collection of Microorganisms's common micro-organisms center preservation, is numbered CGMCCNo.1082.
Particularly Alpha-hemolytic streptococcus D33 bacterial strain behind ground screening, separation and the purification, selects higher, the secreted mannan peptide content of fermentation unit higher high yield, quality strains T33 strain through space treatment mutation.By Institute of Microorganism, Academia Sinica whole-cell protein SDS-polyacrylamide gel (SDS-PAGE) analysis of T33 bacterial strain and D33 bacterial strain and the genomic DNA restricted enzyme cutting analysis (RFLP/PFGE) of bacterial strain are compared, can prove that its gene of T33 bacterial strain that space mutagenesis and ground filter out has variation.This mutant strain is stable in heredity, stronger production adaptability is arranged, the mannan peptide content that is produced by its fermentation improves, content of peptides improves 3 to 5 times than national standard (80%), institute for drug control, Xi'an sample presentation is measured and is reached 271.6%, and fermentation content on average exceeds more than three times than matched group product content.This strain is through the spaceship-carried space flight of Shenzhou series of spacecraft, and further screening and culturing breeding forms stable hereditary property, the tangible high-yield highly-effective strain of variation features to strain by BeiJing ZhongKe Institute of Micro-biology of institute and biology department of Northwest University.The mannan peptide content of α in the every fermentation unit of this strain-space flight strain production has improved more than several times.(the material 1 of seeing Appendix: science and technology bureau Shaanxi Province, Shaanxi Province scientific and technological achievement assay certificate material
Adnexa material 2: the mannatide that the space flight strain is produced is produced bacterial strain and is carried notarization through " No. three, divine boat " airship.
Adnexa material 3: the mannatide that the space flight strain is produced is produced bacterial strain and is returned ground screening report through the lift-launch of " No. three, divine boat " airship
Adnexa material 4: Microbe Inst., Chinese Academy of Sciences produces the form Physiology and biochemistry probation report book of bacterial strain and ground contrast bacterium about the mannatide that " No. three, divine boat " airship carries the production of space flight strain
Adnexa material 5: Microbe Inst., Chinese Academy of Sciences produces SDS-PAGE and the RFLP/PFGE Analysis and Identification statement of bacterial strain and ground contrast bacterium about the mannatide that " No. three, divine boat " airship carries the production of space flight strain
Adnexa material 6: the mannatide oral liquid examining report that institute for drug control, Shaanxi Province " No. three, divine boat " space flight strain is produced
Adnexa material 7: scientific and technological novelty assessment report copy
Adnexa material 8: notice is accepted in China Committee for Culture Collection of Microorganisms's common micro-organisms center preservation culture presevation)
Strain improvement: on the basis of Alpha-hemolytic streptococcus growth rhythm, selected than the proper growth strain in period, adopt the plate growth bacterium colony, immerse methods such as the bacteria suspension in other material, germ-carrying sand, carry " No. three, divine boat " spacecraft on March 25th, 2002.Carried out 6 days 0 18 hours flying at space track (200 kilometers of perigee altitudes, 350 kilometers of altitude of the apogees) at rail.The specific condition of space mainly is presented as special environments such as microgravity, fine vacuum, high radiation, alternating magnetic field.The strain of outer-space flight be placed in one with the diverse environment of tellurian ecological environment in, the electronics, proton and the mental retardation heavy particle that mainly comprise coming self-magnetic field to capture; Cosmic ray such as proton, particle and heavier high energy heavy particle from the milky way galaxy; From the proton of sun magnetic storm and heavy particle etc.These particles act on the dna double chain structure in the microbial cell nuclear, can cause double-strand break.Microgravity, high vacuum environment can make the base sequence of DNA recombinate, promptly genomic reorganization and variation.The new bacterial strain that the variation back produces, variation in various degree all can take place in its morphological characteristic, cultural characteristic, biochemical reactions, metabolite, hereditary character and protein expression, pilot scale production target etc.After ground is returned in spacecraft, through further screening, only optimize wherein 0.2% plus variant and the stable bacterial strain of inherited character, make the production strain through cultivation.This strain that after spaceship-carried mutation, selects December in 2003 29 days by China Committee for Culture Collection of Microorganisms's common micro-organisms center preservation, be numbered CGMCCNo.1082.
Experiment and middle trial production result show, stable on inherited character through the novel space strain behind the space mutagenesis, stronger production adaptability is arranged, the mannan peptide content that is produced by its fermentation improves, content of peptides improves 3 to 5 times than national standard (80%), institute for drug control, Xi'an sample presentation is measured and is reached 271.6%, and fermentation content on average exceeds more than three times than matched group product content, and fermentation period shortens greatly.
Preparation method:
The space flight strain is produced the preparation process of mannatide:
The mannatide of space flight strain of the present invention production is by following method preparation: the space strain preparation--purify, and final production goes out mannatide by one grade fermemtation--second order fermentation-----fermentation liquid.
1. space strain preparation:
With through the Alpha-hemolytic streptococcus of space mutagenesis breeding meticulous selection-breeding as producing strain.
A. inclined-plane seed culture medium: Carnis Bovis seu Bubali cream 0.5%, yeast extract 0.6%, peptone 0.5%, glucose 0.4%, sodium chloride 0.5%, agar 3%, sheep blood 8%; PH7.4.
121 ℃ of inclined-plane seed culture medium sterilising temps, 30 minutes time, steam pressure 0.12Mpa.
Unpacking strain cryovial with aseptic broth bouillon dilution, inserts the blood inclined-plane under aseptic condition, the rearmounted 38 ℃ of constant temperature culture of inoculation 30 hours.
B. meat soup seed culture medium: Carnis Bovis seu Bubali cream 0.5%, yeast extract 0.6%, peptone 0.5%, glucose 0.4%, sodium chloride 0.5%; PH7.4.
121 ℃ of meat soup seed culture medium sterilising temps, 30 minutes time, steam pressure 0.12Mpa.
With cultured slant strains under aseptic condition by 9% inoculum concentration, insert in the meat soup seed culture medium 38 ℃ of constant temperature culture 30 hours.
2. sweat:
Fermentation medium: Carnis Bovis seu Bubali cream 0.4%, yeast extract 0.5%, peptone 0.5%, glucose 0.4%, sodium chloride 0.5%.
121 ℃ of fermentation medium sterilising temps, 30 minutes time, steam pressure 0.12Mpa.
A. one grade fermemtation jar: with good meat soup strain under aseptic condition by 10% inoculum concentration, insert first class seed pot, 29 ℃ of constant temperature culture 30 hours, tank pressure was no more than 0.02Mpa, ventilation is advisable can stir culture fluid, fully stirs continuously.
B. second order fermentation jar: with the one grade fermemtation culture fluid under aseptic condition by 20% inoculum concentration, insert fermentation tank, 29 ℃ of constant temperature culture 70 hours, tank pressure is 0.02Mpa not, jar is put in deactivation.Deactivation is adopted to heat and is made the fermentation liquid temperature reach 100 ℃, is incubated 60 minutes, and cooling is left standstill.
Leaching process:
A, fermentation liquid concentrate, and make concentrated solution volume and fermentating liquid volume ratio be controlled at 1: 15-1: 20 or be determined by circumstances.
The concentrated solution of b, fermentation liquid adds 80-99% ethanol, and the volume ratio is controlled at 1: 1.5-1: 5.5 or be determined by circumstances.Fully stir leave standstill after, centrifugal removal supernatant, the precipitation dissolved in distilled water, accent pH5.0 obtains lysate and lysate is left standstill.
C, the more centrifugal removal impurity of lysate is obtained supernatant, accurately measure the clear liquid volume, calculate required amount of alcohol by the supernatant stereometer, adjust pH slowly joins ethanol in the supernatant, and fully stirs, and leaves standstill the centrifugal removal supernatant in back and obtains precipitate.
D, precipitate reuse dissolved in distilled water are transferred pH, and centrifugal, supernatant adds ethanol precipitation again.Such technology repeatable operation to intermediate detection qualified till, the precipitate that obtains is the mannatide crude product that the space flight strain is produced.Vacuum drying 3-8 hour, promptly obtain the mannan peptide product that the space flight strain is produced.
The check of the product that said method obtains:
[character] this product is white or little yellow amorphous powder; Odorless, tasteless.
This product is easily molten in water, and is insoluble in ethanol, chloroform and acetone.
Specific optical rotation: get this product, accurate claim surely, be dissolved in water and be diluted to the solution that contains 10mg among every 1ml approximately, measure (two appendix vIE of Chinese Pharmacopoeia version in 2000) in accordance with the law, be+70 degree spend to+80 specific optical rotation.
[discriminating] 1, get this product 10mg, add water 0.5ml and make dissolving, add a-naphthols alcoholic solution (5-100) 1ml, shake up, slowly add sulphuric acid 0.5ml along tube wall, after several minutes, the interface is aubergine.
2, get this product, add water and make the solution that contains 1mg among every 1ml, get about 10ul point on filter paper, dry, fix, put high salpeter solution and (get periodic acid 1.2g with dehydrated alcohol, after adding water 30ml dissolving. add 0.2mol/L sodium acetate solution 1.5ml and ethanol 100ml, mixing is promptly.Put the dark place and preserve, can use the several months) the middle immersion 5 minutes, take out, wash with 70% alcoholic solution, (get potassium iodide 5g, sodium thiosulfate 5g adds water 100ml and makes dissolving to put reducing solution, add ethanol 150ml, 2mol/L hydrochloric acid solution 2.5ml again, with adding, face the time spent and join with stirring) the middle immersion 5 minutes, take out, wash with 70% alcoholic solution, put in the pinkish red industry sulphuric acid test solution and soaked about 30 minutes, take out, (get sodium pyrosulfite 0.4g with sodium metabisulfite solution, add hydrochloric acid 1ml, being dissolved in water makes into 100ml, promptly), and flushing, dry, the place should be aubergine at the filter paper point sample.
3, get test sample and reference substance is an amount of, add respectively the chlorination sodium injection make contain 1mg among every 1ml solution as need testing solution and reference substance solution, press the test of mannatide immunogenicity determining method, test sample and contrast QC should all not have haemolysis to be taken place.
[inspection] 1, acidity: get this product, add water and make the solution that contains 10mg among every 1ml, measure (two appendix VIH of Chinese Pharmacopoeia version in 2000) in accordance with the law, pH value should be 3.0-5.0.
2, trap: get this product, add water and make the solution that contains 0.4mg among every 1ml, according to spectrophotography (two appendix VIA of Chinese Pharmacopoeia version in 2000), wavelength place at 260nm, its trap must not be greater than 0.25, and at the wavelength place of 280nm, its trap must not be greater than 0.20.
3, total nitrogen: get this product, measure according to N2 method (two appendix VIID second methods of Chinese Pharmacopoeia version in 2000). press dry product and calculate, contain total nitrogen and should be 0.8-2.0%.
4, immunogenicity: get test sample and reference substance is an amount of, add the chlorination sodium injection respectively and make the solution that contains 10mg among every 1ml, make 1: 2,1: 4,1: 8,1: 16,1: 32,1: 64,1: 128,1: 256 diluent as need testing solution and reference substance solution with phosphate buffer respectively again, check in accordance with the law (attached mannatide immunogenicity determining method) that the least concentration of the insoluble blood vessel of test sample should be higher than more than a times of reference substance respective concentration.
5, loss on drying is got this product, is dried to constant weight at 105 ℃, subtracts weight loss and must not cross 5.0% (two appendix VIIIL of Chinese Pharmacopoeia version in 2000).
6, heavy metal is got this product, at 1.0g, checks that in accordance with the law (Chinese Pharmacopoeia version VIIIH in 2000) contains heavy metal and must not cross 20/1000000ths.
7, the undue toxicity gets this product, adds the chlorination sodium injection and makes the solution that contains 0.5mg among every 1ml, checks (Chinese Pharmacopoeia version appendix in 2000 XIC) in accordance with the law. press the intravenous injection administration, and should (injection) up to specification.
[assay]
1. the preparation of reference substance solution
Precision takes by weighing through 105 ℃ of D-mannose reference substance 0.1g that are dried to constant weight and puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale. shake up; Precision is measured 5ml, puts in the measuring bottle of 100ml, adds water to scale, shakes up. contain mannose 50ug among every 1ml.
2. need testing solution is equipped with
It is an amount of to get this product, and accurate the title decides, and is dissolved in water and makes the solution that contains 40ug among every 1ml.
3. the preparation of standard curve
Precision takes by weighing reference substance solution 0,0.2,0.4,0.6,0.8,1.0ml, put respectively in the tool plug test tube, respectively add water to 1.0ml, add 3% phenol solution 1.0ml again, shake up, pour sulphuric acid 4.5ml, shake up, being positioned over room temperature, is blank with 0 pipe. measure trap according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000) at the wavelength place of 490nm.To corresponding trap, calculate regression equation with mannose ug number.
4. the algoscopy precision is measured need testing solution 1.0ml, and from " adding 3% phenol solution 1.0ml again ", operation is in accordance with the law measured trap, by the content of regression equation calculation mannose under the sighting target directrix curve preparation.
Mannatide immunogenicity determining method (complement combined techniques);
1, test solution
A. phthalate buffer (pH7.2)
Get sodium chloride 8.5g, sodium hydrogen phosphate 0.565g and potassium dihydrogen phosphate 0.135g, add water to 1000ml and make its dissolving, add 10% Adlerika 1ml, shake up.
B.1% sheep erythrocyte suspension
The preparation of sheeps blood erythrocyte: (get glucose 20.5g, sodium citrate 8.0g, sodium chloride 4.2g in filling equivalent A Shi liquid by sheep jugular vein sterile blood sampling, citric acid 5.5g, add water to 1000ml and make dissolving, 100 ℃ the sterilization 30 minutes) sterile chamber in, 4 ℃ of preservations.
The preparation of 1% sheeps blood erythrocyte suspension: it is an amount of to get above-mentioned sheeps blood erythrocyte, and with sodium chloride injection washing three times, each centrifugal 5 minutes (2000 rev/mins), sheeps blood erythrocyte is amassed in pressure, makes 1% sheeps blood erythrocyte suspension with sodium chloride injection.Get suspension, make need testing solution for 20 times with the sodium chloride injection dilution, other gets 20 times of equivalent suspension thin ups as blank solution, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), wavelength place at 541nm measures, its trap should be 0.65-0.70, should regulate the concentration of 1% sheep erythrocyte suspension as overrun.
C. hemolysin and sensitization sheeps blood erythrocyte
The preparation of hemolysin: get above-mentioned hematocrit sheeps blood erythrocyte, make 25% sheeps blood erythrocyte suspension with sodium chloride injection. get 1 of rabbit, the above-mentioned sheeps blood erythrocyte suspension of intravenous injection, once a day, totally seven times, first three time 3ml, three 5ml in back, last is injected blood sampling in back seven days.Separation of serum, 56 ℃ of deactivations in .30 minute, packing is preserved below 0 ℃.
The mensuration of amboceptor unit: it is an amount of to get hemolysin, add phosphate buffer and make 1: 1000,1: 2000,1: 3000,1: 4000,1: 5000,1: 6000,1: 7000,1: 8000,1: 9000,1: 10000 diluent respectively, respectively getting 0.1ml puts in the test tube, add 1% Sanguis caprae seu ovis cell suspension 0.1ml, shake up, add dilution factor and be 1: 30 guinea pig serum (complement) 0.2ml and phosphate buffer 0.2ml, shake up, 37 ℃ of insulations 30 minutes, the high dilution of complete hemolysis pipe is 1 unit hemolysin.
The preparation of sensitization sheeps blood erythrocyte: before facing usefulness, the sheeps blood erythrocyte suspension with 2% mixes with 2 unit haemolysis rope equal-volumes, and 37 ℃ are incubated 15 minutes promptly.
Complement: get the Cavia porcellus more than three, the heart blood sampling, centrifugalize serum is preserved below 0 ℃.
The mensuration of complement unit: it is an amount of to get complement, add phosphate buffer, make 1: 40,1: 60,1: 80,1: 100,1: 120,1: 140,1: 160,1: 180 diluent respectively, respectively get 0.2ml and put in the test tube, add the 0.2ml phosphate buffer, shake up, 37 ℃ of insulations are after 30 minutes, add sensitization sheeps blood erythrocyte 0.2ml respectively, shake up, 37 ℃ are incubated 30 minutes again.The high dilution of complete hemolysis pipe is the complement of 1 unit.
Antibody: it is an amount of to get the mannatide reference substance, add the chlorination sodium injection and make the reference substance solution immunizing rabbit that contains 10mg among every 1ml, the next day adopt ear vein injection reference substance solution once.Inject for the first time 0.2ml, for the second time respectively inject 0.5ml to the 5th time, respectively inject 1.0ml the 6th time to the tenth time, the tenth once respectively injects 2.0ml to the 15 time, and last is injected blood sampling in back three days, centrifugalize serum, 56 ℃ of deactivations in following 30 minutes, (before facing usefulness, needing 56 ℃ of deactivations once more in 30 minutes) preserved in packing below 0 ℃.
The mensuration of antibody unit: it is an amount of to get antibody, add phosphate buffer and make 1: 2,1: 4,1: 8,1: 16,1: 32.1: 64,1: 128 diluent respectively, respectively getting 0.1ml puts in the test tube, add mannatide reference substance solution 0.1ml and the 2 complement 0.2ml of unit, shake up, place more than 4 hours in 4-8 ℃, put 37 ℃ of insulations 30 minutes, the high dilution of insoluble blood vessel is 1 unit antibody.Establish antigen simultaneously and (do not add antibody, replace with the 0.1ml phosphate buffer), antibody (do not add antigen, replace with the 0.1ml phosphate buffer), complement (do not add antigen, antibody, replace with the 0.2ml phosphate buffer) control tube, more than three kinds of control tube haemolysis entirely; The sensitization sheeps blood erythrocyte that other establishes (do not add antigen, antibody and complement, replace with the 0.4ml phosphate buffer) control tube is haemolysis not.
2, immunogenicity determining method
It is an amount of to get rapid glycopeptide reference substance of manna and test sample, make the reference substance solution and the need testing solution of variable concentrations according to the regulation under the medicine item, respectively getting 0.1ml puts in the test tube, add the 2 antibody 0.1ml of unit and the 2 complement 0.2ml. of unit shake up, more than 4 hours, put 37 ℃ of insulations 30 minutes in 4-8 ℃ of placement, add sensitization sheeps blood erythrocyte 0.2ml, shake up, 37 ℃ are incubated 30 minutes again.Observe the haemolysis situation of each pipe, the least concentration of insoluble blood vessel is represented the immunogenicity of mannatide.Establish antigen simultaneously and (do not add antibody, replace with the 0.1ml phosphate buffer), antibody (do not add antigen, replace with the 0.1ml phosphate buffer), complement (do not add antigen, antibody, replace) control tube with the 0.2ml phosphate buffer, more than three kinds of control tube haemolysis entirely: the sensitization sheeps blood erythrocyte that other establishes (do not add antigen, antibody and complement, replace with the 0.4ml phosphate buffer) control tube is haemolysis not.
Embodiment 1 gets Chinese medicine: Radix Codonopsis 60g, Rhizoma Atractylodis Macrocephalae 100g, Pericarpium Citri Reticulatae 150g, Cortex Magnoliae Officinalis 120g, Rhizoma Chuanxiong 60g, Fructus Oryzae Germinatus 120g, Fructus Setariae Germinatus 120g.Chinese medicine through washing, decoction (fried in shallow oil 2 hours for the first time, fried in shallow oil 1 hour for the second time, merge decocting liquid twice), precipitate with ethanol, filtration, concentrated, is added α-mannatide 100g, zinc gluconate 50mg, vitamin B 150mg, B 28mg, B 625mg, it is bottled that the simple syrup seasoning makes 100ml, standby through after the assay was approved.
Concrete production process is produced according to preparation technology's (Chinese Pharmacopoeia Commission compiles, and Chemical Industry Press publishes) of 2000 editions granules of Pharmacopoeia of People's Republic of China.
Just component is different with embodiment 1 for other embodiment, and other production process is identical.
Embodiment 2 components are per 1000 to contain α-mannatide 300g, Radix Glycyrrhizae 150g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 100g, Radix Ginseng 50g, Rhizoma Dioscoreae 100g, Fructus Jujubae 100g, Poria 100g.
Embodiment 3 components are that every 1000g contains α-mannatide 300g, Radix Glycyrrhizae 50g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 50g, Radix Ginseng 45g, Rhizoma Dioscoreae 50g, Fructus Jujubae 50g.Poria 30g, Rhizoma Atractylodis Macrocephalae 35g, Polyporus 30g, Rhizoma Alismatis 30g, Radix Aucklandiae 35g, Fructus Amomi 30g, Folium Perillae 55g, Pericarpium Arecae 50g, Cortex Mori 30g, Fructus Chaenomelis 30g.
Embodiment 4 components are per 1000 to contain α-mannatide 200g, Radix Glycyrrhizae 50g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 25g, Radix Astragali 25g, Radix Ginseng 25g, Rhizoma Dioscoreae 50g, Fructus Jujubae 50g, Poria 25g, Rhizoma Atractylodis Macrocephalae 15g, Polyporus 15g, Rhizoma Alismatis 20g, Radix Aucklandiae 25g, Fructus Amomi 20g, Folium Perillae 45g, Pericarpium Arecae 30g, Cortex Mori 30g, Fructus Chaenomelis 30g, Semen Persicae 20g, Flos Carthami 20g, rhizoma sparganic 20g, Rhizoma Curcumae 20g, Herba Lycopi 20g, Lignum Sappan 20g, Herba Artemisiae Anomalae 20g, Herba Leonuri 25g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 25g, Myrrha 20g.
Embodiment 5 components are that every 1000g contains α-mannatide 200g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g.
Embodiment 6 components are that every 1000g contains α-mannatide 150g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g, vitamin (B1, B2, B6) 50g.
Embodiment 7 components are that every 1000g contains α-mannatide 130g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g, vitamin (B1, B2, B6) 20g, zinc sulfate 50g.
The compound mixture toxicological study of treatment infantile anorexia of the present invention: 1. acute toxicity test: the once oral 100ml of rabbit, do not see dead and any untoward reaction; 2. subacute toxicity test: rabbit is oral, each 30ml, and every day three times, hepatic and renal function, hemogram and all no abnormal variation of each organs and tissues are checked in logotype 2 months; 3. the Cavia porcellus hypersensitive test is negative; 4. the deadly test of teratogenesis is all negative.
The animal pharmacodynamic experiment:
Animal: test with totally 60 of SD rats (providing) by Xi'an Jiaotong University Medical College's Experimental Animal Center, age in days 35-40g, body weight (60 ± 10) g, male and female half and half are divided into ten groups at random, every group each 6.
The preparation of infantile anorexia animal model: special feedstuff adopts mixing in proportion such as the delicatessen food of using dried fish floss, milk powder, analysis for soybean powder, white sugar, fresh hen egg, pinches into the cookies shape, and every about 20g dries, cold preservation.Control rats is fed conventional Mus feedstuff, and rat model is fed homemade special 4 weeks of feedstuff, and all single cage of two treated animals is raised, the ad lib water inlet.
The experiment grouping: this test divides ten groups and carries out.
1. matched group: whole experiment is all normally fed, and does not apply any intervening measure.
2. model group: the rat in special 4 weeks of forage feed.
3. α-mannatide oral liquid treatment group: anorexia rat model+α-mannatide oral liquid is irritated stomach, each 5ml, every day three times, 1 week of logotype.
4. Zinc Gluuconate Oral Solution treatment group: anorexia rat model+Zinc Gluuconate Oral Solution is irritated stomach, each 5ml, every day three times, 1 week of logotype.
5. first kind of compound mixture treatment group of the present invention: anorexia rat model+first kind of compound mixture of the present invention irritated stomach, each 5ml, every day three times, 1 week of logotype.
6. second kind of compound mixture treatment group of the present invention: anorexia rat model+second kind of compound mixture of the present invention irritated stomach, each 5ml, every day three times, 1 week of logotype.
7. the third compound mixture treatment group of the present invention: anorexia rat model+the third compound mixture of the present invention is irritated stomach, each 5ml, every day three times, 1 week of logotype.
8. the 4th kind of compound mixture treatment group of the present invention: anorexia rat model+the 4th kind of compound mixture of the present invention irritated stomach, each 5ml, every day three times, 1 week of logotype.
9. the 5th kind of compound mixture treatment group of the present invention: anorexia rat model+the 5th kind of compound mixture of the present invention irritated stomach, each 5ml, every day three times, 1 week of logotype.
10. the 6th kind of compound mixture treatment group of the present invention: anorexia rat model+the 6th kind of compound mixture of the present invention irritated stomach, each 5ml, every day three times, 1 week of logotype.
Experimental drug product and reagent:
α-mannatide oral liquid: provide by our company.
Zinc Gluuconate Oral Solution: commercially available prod.
Six kinds of compound mixtures of the present invention: provide by our company.
Blood plasma CCK-8 (CCK-8) radioimmunological kit: adopt American I NCSTAR company product.
Blood plasma cheese neuropeptide (NPY) radioimmunological kit: adopt U.S. SIGMA company product.Blood plasma neurotensin (NT) radioimmunological kit: adopt U.S. SIGMA company product.
The mensuration of experimental index:
The mensuration of rat food ration: after one week of medication, write down 24 hours food ration of all rats, and carried out statistical analysis (seeing Table 1) in the 8th day with SIGMASTAT software.
The assay of CCK-8, NPY and NT in the rat plasma: surveyed after the food ration all rat fasting 12 hours, broken end is got blood on an empty stomach, with EDTA-Na 2Anticoagulant, separated plasma ,-20 ℃ of following stored frozen are to be measured, the content of CCK-8 (table 2), NPY (table 3) and NT (table 4) in the employing measured by radioimmunoassay blood plasma, the operating procedure strictness is undertaken by the medicine box description, and the gained experimental data is carried out statistical analysis with SIGMASTAT software.
Experimental result:
Table 1: each organizes the per day food ration of rat (g, X ± s)
Group Food ration
Control group model group α-mannosans peptides oral liquor treatment group Zinc Gluuconate Oral Solution treatment group first kind of compound mixture treatment group second compound mixture of the present invention treatment group the third compound mixture treatment group of the present invention the 4th kind of compound mixture treatment group of the present invention the 5th kind of compound mixture treatment group of the present invention the 6th kind of compound mixture treatment group of the present invention of the present invention ????19.17±3.26 ????13.32±1.85 **????15.27±1.32 *????15.46±1.06 *????18.05±1.35 ????18.20±1.24 ????18.37±1.09 ????18.53±1.45 ????18.92±1.34 ????19.15±1.04
Annotate: compare with matched group *P＜0.05, *P＜0.01
The data show of last table: compare with control rats, the day food ration of anorexia model group rat significantly reduces (P＜0.01); The food ration of α-mannatide oral liquid treatment group and Zinc Gluuconate Oral Solution treatment group rat significantly improves (P＜0.05) than model group, but still is starkly lower than matched group (P＜0.05), does not have significant difference between two kinds of Therapeutic Method; The food ration of six kinds of compound mixture treatment group rats of the present invention all significantly improves (P＜0.01) than model group, and the trend that increases is gradually arranged, and does not have significant difference with matched group.
Above experimental result shows: anorexia rat food ration obviously is less than normal rat; Six kinds of compound mixtures of the present invention all can improve the appetite of anorexia rat, make it recover normal, and along with comprehensive gradually therapeutical effect of prescription is also more remarkable; α-mannatide oral liquid and Zinc Gluuconate Oral Solution have some improvement to the appetite of anorexia rat, but curative effect is starkly lower than six kinds of compound mixtures of the present invention.
Table 2: each organizes content (ng/L, the X ± s) of rat plasma CCK-8
Group ????CCK-8
Control group model group α-mannosans peptides oral liquor treatment group Zinc Gluuconate Oral Solution treatment group first kind of compound mixture treatment group second compound mixture of the present invention treatment group the third compound mixture treatment group of the present invention the 4th kind of compound mixture treatment group of the present invention the 5th kind of compound mixture treatment group of the present invention the 6th kind of compound mixture treatment group of the present invention of the present invention ????253.75±95.09 ????506.88±113.32 **????409.71±79.14 *????410.13±85.06 *????267.07±62.75 ????260.35±59.12 ????258.31±47.32 ????255.06±67.45 ????250.71±70.16 ????246.57±67.46
Annotate: compare with matched group *P＜0.05, *P＜0.01
CCK-8 is a kind of at gastrointestinal tract and the extensive peptide hormone that distributes of cerebral tissue, has significantly to cause anoretic effect.Above experimental data shows: model group rat plasma CCK-8 content raises significantly than matched group, reach 506.88 ± 113.32, compared significant difference (P＜0.01) with matched group, show that the nursing of Long-term High-fat high protein feed can make animal maincenter and periphery CCK-8 secretion increasing, CCK-8 increases the principal element that suppresses animal ingestion just, and this link plays an important role in the morbidity of infantile anorexia; After six kinds of compound mixtures treatment of the present invention, rat plasma CCK-8 content returns to again near normal level, and curative effect is more remarkable with the reinforcement of prescription, with matched group no significant difference (P＞0.05), show that six kinds of compound mixtures of the present invention all can effectively reduce the content of anorexia rat plasma CCK-8, improve the anorexia that it causes; The content of α-mannatide oral liquid treatment group and Zinc Gluuconate Oral Solution treatment group rat plasma CCK-8 significantly is lower than model group rat (P＜0.05), also be significantly higher than simultaneously control rats (P＜0.05), show that list has some improvement to anorexia with α-mannatide oral liquid and Zinc Gluuconate Oral Solution, but effect can not show a candle to six kinds of compound mixtures of the present invention.
Above experimental result shows: the content of anorexia rat plasma CCK-8 obviously raises, and six kinds of compound mixtures of the present invention all can effectively reduce the content of anorexia rat plasma CCK-8, and make it return to normal level; α-mannatide oral liquid and Zinc Gluuconate Oral Solution have some improvement to anorexia rat plasma high level CCK-8, but the amplitude that reduces is smaller, normal plasma C CK-8 level is still higher, and curative effect is starkly lower than six kinds of compound mixtures of the present invention.
Table 3: each organizes content (pg/ml, the X ± s) of rat plasma NPY
Group ????NPY
Control group model group α-mannosans peptides oral liquor treatment group Zinc Gluuconate Oral Solution treatment group first kind of compound mixture treatment group second compound mixture of the present invention treatment group the third compound mixture treatment group of the present invention the 4th kind of compound mixture treatment group of the present invention the 5th kind of compound mixture treatment group of the present invention the 6th kind of compound mixture treatment group of the present invention of the present invention ????231.90±71.00 ????142.41±49.78 *????138.17±59.46 *????140.09±67.34 *????219.20±76.13 ????223.79±69.41 ????227.67±67.12 ????230.69±71.03 ????231.78±56.34 ????235.41±59.36
Annotate: compare with matched group *P＜0.05
NPY is a kind of braingut petide that is present in the genus pancreatic polypeptide family of nervus centralis, enteric nervous and sympathetic nervous system, and it is the strong stimulation agent of ingesting, and it produces by modulation of appetite maincenter functional activity the strong stimulation of ingesting.Above experimental data shows: the content of anorexia rat plasma NPY obviously reduces (P＜0.05) than matched group, show that NPY exists with low concentration in anorexia rat cerebral tissue, thereby cause " braingut petide-appetite center " dysfunction, reduced stimulation ingesting; After six kinds of compound mixtures treatment of the present invention, the content of anorexia rat plasma NPY raises successively, and and matched group between no significant difference, return to normal level, show that six kinds of compound mixtures of the present invention have unique therapeutical effect to " braingut petide-appetite center " dysfunction of anorexia rat, and along with the reinforcement therapeutic effect of prescription is also become better and better; The changes of contents of α-mannatide oral liquid treatment group and Zinc Gluuconate Oral Solution treatment group rat plasma NPY is not obvious, shows single with α-mannatide oral liquid and the Zinc Gluuconate Oral Solution poor effect of improving to anorexia rat " braingut petide-appetite center " dysfunction.
Above experimental result shows: anorexia rat plasma NPY content obviously reduces, and " braingut petide-appetite center " dysfunction weakens the stimulation of ingesting; Six kinds of compound mixtures of the present invention all can effectively improve the content of blood plasma NPY, recover it stimulation of ingesting is reached normal level, and are evident in efficacy; And single the content of anorexia rat plasma NPY is not had obvious change with α-mannatide oral liquid and Zinc Gluuconate Oral Solution, the function of anorexia rat " braingut petide-appetite center " still is in disturbance state, and the curative effect of these two kinds of medicines is starkly lower than six kinds of compound mixtures of the present invention.
Table 4: each organizes content (pg/ml, the X ± s) of rat plasma NT
Group ????NT
Control group model group α-mannosans peptides oral liquor treatment group Zinc Gluuconate Oral Solution treatment group first kind of compound mixture treatment group second compound mixture of the present invention treatment group the third compound mixture treatment group of the present invention the 4th kind of compound mixture treatment group of the present invention the 5th kind of compound mixture treatment group of the present invention the 6th kind of compound mixture treatment group of the present invention of the present invention ????52.41±24.86 ????94.33±21.23 *????88.23±20.26 *????90.14±26.79 *????63.42±22.36 ????60.24±23.15 ????57.46±19.71 ????55.38±21.54 ????51.63±22.45 ????50.89±18.73
Annotate: compare with matched group *P＜0.05
NT is a kind of single chain polypeptide that contains 13 amino acid residues, it is secreted by a kind of special endocrine cell that are called the N cell, and it is inhibited to the stomach motion, can delay gastric emptying, gastrocolic reflex there is regulating action, and can gastric acid inhibitory and pepsic secretion.Above experimental result shows: the content of anorexia rat plasma NT is than matched group obviously raise (P＜0.05), show that NT increases in the gastrointestinal distribution, aggravated gastrointestinal motility dysfunction, thereby delayed gastric emptying, owing to suppressed gastric acid and pepsic secretion, influenced the digestive function of rat simultaneously; After six kinds of compound mixtures treatment of the present invention, the content of anorexia rat plasma NT significantly reduces, return to normal level, and, show that six kinds of compound mixtures of the present invention are to anorexia rat gastrointestinal motility dysfunction and the bad therapeutical effect that uniqueness is arranged of digestive function along with the also reinforcement gradually of curative effect comprehensively gradually of prescription; And the changes of contents of α-mannatide oral liquid treatment group and Zinc Gluuconate Oral Solution treatment group rat plasma NT is not obvious, gastrointestinal motility function and the digestive function of rat still are in failure condition, show singly to use α-mannatide oral liquid and the Zinc Gluuconate Oral Solution unsatisfactory curative effect to the rat apositia.
Above experimental result shows: the normal rat of the content of anorexia rat plasma NT significantly raises, and the gastrointestinal motility dysfunction of rat, digestive function are also bad; After six kinds of compound mixtures treatment of the present invention, the content of rat plasma NT returns to normal level, and gastrointestinal motility function and digestive function are normal, and six kinds of compound mixtures of the present invention are all remarkable to the curative effect of apositia; And single the content of anorexia rat plasma NT is not had obvious change with α-mannatide oral liquid and Zinc Gluuconate Oral Solution, apositia there is not obvious curative effects.
The clinical efficacy checking of treatment infantile anorexia compound mixture of the present invention: in so-and-so, man, 3 years old.Anorexia 2 years, daily inleting appetite be (about 2 liang) seldom.Infant is the appetite extreme difference since the childhood, and how not ante cibum the desire feed, each feed, and a food is promptly full, eats cold drinks and snachs and sweet food well.Emaciated physique is hard and dry, and shallow complexion is simple and unadorned, and often easily ill, as: flu, fever, cough etc.Often take appetizing, spleen invigorating, digestant medicine and health product usually, and paid close attention to the absorption of control cold drinks and snachs and sweet food since the idiopathy.But do not seen since 2 years and be clearly better.Take Chinese medicine and western medicine compound mixture treatment of the present invention after three days, appetite promptly takes a turn for the better to some extent, and dietary amount also increases to some extent, reaches about 4 liang.Continuously after a treatment course of treatment (two weeks were a course of treatment), appetite increases, and dietary amount reaches 6-8 two, and has rosy cheeks, and passive protective physical fitness strengthens, follow up a case by regular visits to do not catch a cold half a year, have a fever, disease such as cough, weight increase 5 kilograms.
The curative effect statistics of treatment infantile anorexia compound mixture of the present invention: 88 routine outpatient service infantile anorexia infants are collected in this research altogether, and inappetence or anorexia are in various degree all arranged.Wherein body is than normal youngster's slight of stature, and body weight is lower than normal youngster person's 82 examples; Normal person's 65 examples of spirit; Hypotrichosis jaundice or as fringe knot person 53 examples; Xerostomia is liked drinking-water yearningly, xerosis cutis person's 75 examples; Easy perspiration easy catching a cold person 28 examples.All infants are taken compound mixture of the present invention, every day three times, each 10ml, two courses of treatment of logotype.Criterion of therapeutical effect: if appetite is often become a full member, weight increase is looked into serum zinc＞110 μ mol/L, is recovery from illness; Appetite obviously increases, and other sings and symptomses obviously improve, and looks into serum zinc＞100 μ mol/L, is produce effects; Appetite does not have symptom such as preceding after obvious improvement or the drug withdrawal, looks into serum zinc＜90 μ mol/L, for invalid.The result: by above-mentioned criterion of therapeutical effect, recovery from illness 75 examples account for 85.23% among the 88 routine patients; Produce effects 13 examples account for 14.77%; The statistics total effective rate is 100%.Show the truly have unique curative effect of compound mixture of the present invention to infantile anorexia.
Confirm that through collecting the patient medical record data further investigation conclusion summary of taking medicine in a large number this Chinese medicine and western medicine compound preparation has: 1. coordinate " braingut petide-appetite center " regulatory function to ingesting, " braingut petide-appetite center " is to the regulating action of having ingested, periphery and maincenter braingut petide parasecretion influence the appetite center functional activity, and then influence trophic behavior,, i.e. " braingut petide-appetite center " dysfunction is the important step that development takes place infantile anorexia.2. invigorating the spleen and regulating the stomach promotes gastric secretion, strengthens gastric activity, improves stomach, intestinal tension force, strengthens the effect of dyspepsia and intestinal stasis relieving.3. improve the abnormal symptom of sense of taste olfactory sensation, regulate the body metabolism, quicken bone growth and intellectual development.4. enhancing human body immunity function.5. replenish that body lacks but to vital zinc element of normal physiological metabolism and vitamin B group.

Claims (10)

1, a kind of medicine for the treatment of infantile anorexia is characterized in that: its composition mainly comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 60-90%.
2, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: its composition also comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 30-60%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-40%.
3, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: its composition also comprises α-mannatide 10-40%, air making-up and spleen enlivening class Chinese medicine 10-40%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-40%.
4, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%.
5, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%, vitamin (B1, B2, B6) 2-5%.
6, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: its composition also comprises α-mannatide 10-30%, air making-up and spleen enlivening class Chinese medicine 10-30%, regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine 10-30%, blood-activating and qi-promoting class Chinese medicine 10-30%, promoting digestion and removing stagnation class Chinese medicine 10-30%, vitamin (B1, B2, B6) 2-5%, zinc sulfate 5-10%.
7, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: described air making-up and spleen enlivening class Chinese medicine has: Radix Glycyrrhizae, the Rhizoma Atractylodis Macrocephalae, Radix Codonopsis, the Radix Astragali, Radix Ginseng, Rhizoma Dioscoreae, Fructus Jujubae, Poria; Regulating qi-flowing for strengthening spleen removing dampness class Chinese medicine has: Poria, the Rhizoma Atractylodis Macrocephalae, Polyporus, Rhizoma Alismatis, the Radix Aucklandiae, Fructus Amomi, Folium Perillae, Pericarpium Arecae, Cortex Mori, Fructus Chaenomelis; Blood-activating and qi-promoting class Chinese medicine has: Semen Persicae, Flos Carthami, rhizoma sparganic, Rhizoma Curcumae, Herba Lycopi, Lignum Sappan, Herba Artemisiae Anomalae, Herba Leonuri, cattle lacquer, Hirudo, Tabanus, Olibanum, Myrrha; Promoting digestion and removing stagnation class Chinese medicine has: crataegus pin natifida var. Major, Fructus Hordei Germinatus, Fructus Setariae Germinatus, Massa Medicata Fermentata, Endothelium Corneum Gigeriae Galli, Herba Pogostemonis, Rhizoma Alpiniae Officinarum, Semen Alpiniae Katsumadai, Fructus Amomi, Semen Myristicae, the Radix Aucklandiae, Rhizoma Zingiberis Recens, Fructus Schisandrae Chinensis.
8, a kind of medicine for the treatment of infantile anorexia according to claim 1, it is characterized in that: described medicament per 1000 contains α-mannatide 300g, Radix Glycyrrhizae 150g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 100g, Radix Ginseng 50g, Rhizoma Dioscoreae 100g, Fructus Jujubae 100g, Poria 100g.
9, a kind of medicine for the treatment of infantile anorexia according to claim 1, it is characterized in that: the every 1000g of described medicament contains α-mannatide 300g, Radix Glycyrrhizae 50g, Rhizoma Atractylodis Macrocephalae 50g, Radix Codonopsis 50g, Radix Astragali 50g, Radix Ginseng 45g, Rhizoma Dioscoreae 50g, Fructus Jujubae 50g.Poria 30g, Rhizoma Atractylodis Macrocephalae 35g, Polyporus 30g, Rhizoma Alismatis 30g, Radix Aucklandiae 35g, Fructus Amomi 30g, Folium Perillae 55g, Pericarpium Arecae 50g, Cortex Mori 30g, Fructus Chaenomelis 30g.
10, a kind of medicine for the treatment of infantile anorexia according to claim 1 is characterized in that: the every 1000g of described medicament contains α-mannatide 130g, Radix Glycyrrhizae 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Codonopsis 20g, Radix Astragali 20g, Radix Ginseng 20g, Rhizoma Dioscoreae 30g, Fructus Jujubae 30g, Poria 15g, Rhizoma Atractylodis Macrocephalae 10g, Polyporus 10g, Rhizoma Alismatis 5g, Radix Aucklandiae 15g, Fructus Amomi 20g, Folium Perillae 35g, Pericarpium Arecae 20g, Cortex Mori 25g, Fructus Chaenomelis 25g, Semen Persicae 15g, Flos Carthami 20g, rhizoma sparganic 15g, Rhizoma Curcumae 10g, Herba Lycopi 10g, Lignum Sappan 15g, Herba Artemisiae Anomalae 20g, Herba Leonuri 15g, cattle lacquer 20g, Hirudo 20g, Tabanus 20g, Olibanum 15g, Myrrha 10g, crataegus pin natifida var. Major 20g, Fructus Hordei Germinatus 20g, Fructus Setariae Germinatus 20g, Massa Medicata Fermentata 20g, Endothelium Corneum Gigeriae Galli 15g, Herba Pogostemonis 15g, Rhizoma Alpiniae Officinarum 20g, Semen Alpiniae Katsumadai 20g, Fructus Amomi 20g, Semen Myristicae 20g, Radix Aucklandiae 20g, Rhizoma Zingiberis Recens 15g, Fructus Schisandrae Chinensis 20g, vitamin (B1, B2, B6) 20g, zinc sulfate 50g.
CNB2004101044338A 2003-12-31 2004-12-19 Medicine for treating infantile anorexia Expired - Fee Related CN100360179C (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100341560C (en) * 2005-12-30 2007-10-10 张舒亚 Chinese medicinal preparation for treating chronic gastritis using spleen fortifying oral liquid and stomach fortifying capsule combined treatment
CN102526373A (en) * 2012-01-13 2012-07-04 陈波 Medicinal composition for treating infantile anorexia
CN102671173A (en) * 2012-05-17 2012-09-19 李承平 Medicine compound tablet for infant splenoasthenic diarrhea
CN102698144A (en) * 2012-06-15 2012-10-03 徐州金牌药业有限公司 Traditional Chinese medicine composition for treating gasteremphraxis
CN102743683A (en) * 2012-07-30 2012-10-24 邹晓刚 Traditional Chinese medicine preparation for treating child anorexia
CN103816249A (en) * 2014-03-19 2014-05-28 王秀娟 Chinese medicament for treating infantile anorexia with spleen and stomach qi deficiency
CN104206837A (en) * 2014-08-16 2014-12-17 严中明 Pig fattening additive

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CN1051714C (en) * 1995-11-22 2000-04-26 太极集团涪陵制药厂 Traditional Chinese patent medicine for strengthening spleen and appetizing and its preparation method
CN1429558A (en) * 2003-01-24 2003-07-16 海南豪迈医药有限公司 Mannosan peptide injection and its preparation and use method

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100341560C (en) * 2005-12-30 2007-10-10 张舒亚 Chinese medicinal preparation for treating chronic gastritis using spleen fortifying oral liquid and stomach fortifying capsule combined treatment
CN102526373A (en) * 2012-01-13 2012-07-04 陈波 Medicinal composition for treating infantile anorexia
CN102671173A (en) * 2012-05-17 2012-09-19 李承平 Medicine compound tablet for infant splenoasthenic diarrhea
CN102698144A (en) * 2012-06-15 2012-10-03 徐州金牌药业有限公司 Traditional Chinese medicine composition for treating gasteremphraxis
CN102743683A (en) * 2012-07-30 2012-10-24 邹晓刚 Traditional Chinese medicine preparation for treating child anorexia
CN102743683B (en) * 2012-07-30 2013-12-25 邹晓刚 Traditional Chinese medicine preparation for treating child anorexia
CN103816249A (en) * 2014-03-19 2014-05-28 王秀娟 Chinese medicament for treating infantile anorexia with spleen and stomach qi deficiency
CN104206837A (en) * 2014-08-16 2014-12-17 严中明 Pig fattening additive

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