CN102285958A - Dopamine polymer as well as derivative, preparation method and medicinal purpose thereof - Google Patents
Dopamine polymer as well as derivative, preparation method and medicinal purpose thereof Download PDFInfo
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Abstract
The invention relates to a dopamine polymer as well as derivatives, a preparation process, purposes and a composition thereof, wherein the dopamine polymer as well as derivatives in a cicada slough have the actions of treating Parkinson's disease, resisting convulsion, treating neurodegenerative diseases, eliminating heat and relieving pain, resisting anaphylactic reaction, resisting allergic reaction, treating angina and hoarseness, protecting the liver, regulating lipid and lowering sugar, promoting digestion, resisting tumors, resisting ageing and the like.
Description
Technical field:
The invention belongs to pharmaceutical field, relate to the effective constituent of from cicada slough, separating preparation, particularly relate to separation obtains from cicada slough Dopamine HCL polymer and its derivative, and preparation technology, medicine food purposes and composition.
Background technology:
Cicada slough, head is stated from " Mingyi Bielu ", and original name grasshopper cicada shell has another name called withered cicada, and a volt worm educates.There is the name of cicada slough " property of medicine opinion " beginning.Be called that cicada moves back, periostracum cicada later age again.This product is the nymph of the black grasshopper Cryptotympana pustulata Fabricius of cicada exuviae shell when sprouting wings
[1]Another name periostracum cicada, cicada move back, cicada shell, PERIOSTRACUM CICADAE.Main product in Shandong, Henan, Hebei, Jiangsu etc., also produce in national most of area
[2]Summer, Qiu Erji collect, and remove silt, dry.Cold in nature, it is salty to distinguish the flavor of, and is pungent and cold medicine for relieving the exterior syndrome; Have wind and heat dispersing, improving acuity of vision and removing nebula, promoting eruption is antipruritic, relieving convulsion spasmolysis, effects such as relieving sore throat and diminishing swelling.Can treat common cold due to wind-heat clinically, various inflammation, convulsion with spasms, swelling and pain in the throat, indications such as acne rash furunculosis.Along with science and technology development, its effect constantly is found, and effect is obvious, as anticancer, analgesia, anticonvulsion, antianaphylaxis etc.
Pharmaceutical research shows that cicada slough has following pharmacology and biological activity:
1 anticonvulsant action: treat various epilepsy at Chinese medical discrimination with joining cicada slough in square, especially in the early treatment of traumatic epilepsy, control convulsions effect is rather good.Modern pharmacology experiment showed, that cicada slough alcohol extract and aqueous extract all have anticonvulsant action, and wherein the direct repression of aqueous extract significantly (reduces the mice convulsion incidence), and anticonvulsant action intensity obviously is better than alcohol extract
[6]Because main component is water-soluble amino acids, polyose and various trace elements in the cicada slough.Once had the people that the amino acid composition of cicada slough was done to analyze, anticonvulsant pharmacological action is arranged, the calcium that high level is measured in its trace element analysis test is relevant with anticonvulsant action with aluminium
[7]Its fat-soluble component is less, is bringing into play effects such as anti-oxidant, anti-inflammatory
[6]
2 sedative effects: cicada slough has significant sedative effect, can significantly reduce normal mouse spontaneous activity, and the excitation of antagonism caffeine has synergy with Sodital class medicine.Abdominal injection cicada slough extracting solution can make the movable minimizing of rabbit, peace and quiet.Abdomen and four limbs muscular tension reduce, righting reflex is blunt etc., should act on more obvious during intravenously administrable
[2]
3 analgesic activities: the mouse writhing method measurement result proves that cicada slough each several part extract is pressed the 39g/kg subcutaneous injection respectively, and except that cicada slough head, sufficient analgesia were renderd a service gently, cicada slough integral body and health all had significant analgesia role
[2]
4 refrigeration functions: to the heating rabbit due to the expired Corynebacterium diphtheriae, cicada slough decoction 1g/kg irritates stomach certain refrigeration function
[8]On Carrageenan pyrogenicity rat also has refrigeration function significantly in addition.
5 antibechics, eliminate the phlegm, antiasthmatic effect: the cicada slough extracting solution can obviously prolong cough latent period; Cavy is drawn to breathe heavily and obviously prolongs latent period
[12], have the effect of significantly relievining asthma; Phenol red excretion amount (being tracheae section expectoration amount) increases
[9]Gavage the performance of the sensitization bronchus of rat of Periostracum Cicadae extract and lung tissue inflammatory be improved significantly
[10-12]
6 antiviral and inducement interferon effects: experiment shows that anti-crime diffusing (cicada slough, stiff silkworm, turmeric, rheum officinale, betel nut, the bark of official magnolia, tsaoko, the root of large-flowered skullcap, the wind-weed, rattletop) has tangible antivirus action on cell cultures.Anti-crime is loose and is also had certain inducement interferon effect.Anti-crime is loose the NDV inducement interferon is had obvious facilitation
[2]
7 immunosuppressive actions: the cicada slough extracting solution can obviously alleviate the weight of immune organ thymus gland and spleen.Prove that with the chicken red blood cell method cicada slough liquid obviously reduces the peritoneal macrophage function, send out mensuration through the mouse carbon clearance, the cicada slough extracting solution obviously reduces carbon clearance speed
[6]Experiment shows that cicada slough has restraining effect to non-specific immunity, and IV allergic reaction type and body cell immunologic function are also had obvious restraining effect
[7]
8 anti-allergic effects: cicada slough has the obvious suppression effect to mouse ear xenogenesis passive cutaneous anaphylaxis (PCA), to 2,4-dinitrochlorobenzene (DNCB) induced mice ear delayed type hypersensitivity also has the obvious suppression effect, can reduce the percentage of rat cranial periosteum mastocyte grain very significantly, has stable mast cell membrane, block sensitive media and discharged, suppressed allergic effect
[2] [7]
9 antitumor actions: the in vivo test of cicada slough aqueous extract mouse shows that cicada slough shows the anti-tumor activity of height to ehrlich's ascite cell
[3]After its composition is purified, measures and find to be macromolecular compound.Optionally anticancer growth and do not influence normal cell of cicada slough in cell in vitro is cultivated
[2]
10 toxic side effecties: the cicada slough alcohol extract is injected to mouse peritoneal, observes the death toll in the 24h, records LD
50Be 809 ± 41.8mg/kg.Oral dose reaches 8000mg/kg and does not see death.The cicada slough alcohol extract does not have anaphylaxis, no hemolytic action
[2,4]
11 other effects: intravenous injection cicada slough alcohol extract does not make significant difference, but heart rate is obviously slowed down rabbits blood pressure, breathing
[2]In addition, the cicada slough alcohol extract has the certain protection effect to erythrocyte membrane
[6], can reduce the permeability of mouse peritoneal capillary vessel
[4], can block sympathetic ganglionic conduction on the cat neck, adrenergic receptor and vagusstoff step-down reaction there are not influence
[2]
In view of the cicada slough clinical application is comparatively extensive, newly be used for the multiple disease of each section such as inside and outside, neural, youngster, skin, face, satisfactory effect.Its flavor is sweetly easily accepted by children's when paediatrics is used.Along with the modern pharmacology progress of research, for clinical rational drug use provides theoretical foundation.But its pharmacological research still there is blank, still indeterminate to its mechanism of action.
And not deep enough to this product The Chemical Constituents and application at present yet, its fat-soluble part The Chemical Constituents is still belonged to blank, only find wherein to contain a large amount of chitins and protein, amino acid, organic acid
[2]Cicada slough includes chitin, pteridine class pigment: different xanthin petrin, red pterin, protein, amino acid, organic acid, phenolic compound.Amino acids, wherein total free aminoacids is 12 kinds, comprises aspartic acid, Threonine, L-glutamic acid, L-Ala, glycine, Gelucystine, Xie Ansuan, Isoleucine, leucine, phenylalanine, Methionin, arginine; 17 kinds of hydrolysis amino acids reach Serine, methionine(Met), tyrosine, Histidine, proline(Pro) etc.
[3]And contain solubility calcium
[2]Chitin that extracts from cicada slough and saccharan, MP and IR identify, and have carried out suitability for industrialized production, for medical makeup and foodstuffs industry widespread use
[4]Contain 24 kinds of trace elements in the cicada slough, the content of aluminium is the highest, secondly is calcium, iron, zinc, manganese, phosphorus, magnesium
[5]
But above chemical ingredients is common trophicity composition, is not cicada slough treatment Parkinson's disease, anticonvulsion, nervous headache, dizzy, nerve degenerative diseases, nameless high-fever disappears, analgesic, antianaphylaxis, anti-allergic, analgesia, rubella, itch, the hot eyes ocular, convulsion with spasms, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, the pharyngalgia hoarsen, the hot eyes ocular, itch, protect the liver, transfer blood fat, hypoglycemic, promote gastric secretion, appetite stimulator, improve digestive function, antitumor, immunostimulant, antioxygenation, antidotal effective constituent.
This research has found that by the chemistry and the pharmaceutical research of system separating Dopamine HCL polymer and its derivative of obtaining in the cicada slough brings into play the effective constituent of various therapeutic actions for it.By independent use or add various pharmaceutical adjuncts (various solid preparations, liquid preparation, gel preparation, sustained-release preparation etc.), or with other drug matching, thereby realized that it is in medicine, functional food, healthcare products and Application in Food.
Summary of the invention:
The compound that the object of the present invention is to provide a class to obtain through extraction separation from cicada slough, described compound are Dopamine HCL polymer and its derivative.
Compound of the present invention, be selected from cicada slough amine A and derivative thereof, cicada slough amine B and derivative thereof, cicada slough amine C and derivative thereof, cicada slough amine D and derivative thereof, cicada slough amine E and derivative thereof, cicada slough amine F and derivative thereof, cicada slough amine G and derivative thereof, cicada slough amine H and derivative thereof, cicada slough amine I and derivative thereof, any one compound in cicada slough amine J and derivative thereof and cicada slough amine K and the derivative thereof.Their structure exists with polymer form, and the latter is Duoed a polymer monomer than the former, is the double focusing thing as cicada slough amine A, and cicada slough amine B is a trimer, and by that analogy, cicada slough amine K is 12 polymers.And classes of compounds exists different substituting groups, polymeric position isomerism, polymeric along various derivatives such as (cis) anti-(trans) isomery and glucosides replacements.
Cicada slough amine A of the present invention has skeleton structure shown in the structural formula 1,
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2R3R and 2S3S wherein.
2) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 1-amino-ethyl, the amino straight or branched alkyl that replaces; Wherein optimum is hydrogen, 2-amino-ethyl.And comprise: above substituent amino is by formylation, benzoylation, phenylacetylization, the para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, the acetylize of 4-hydroxy 3-methoxybenzene, 3, the acetylize of 4-dimethoxy benzene, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene.
3) R
3Be hydrogen, methyl, dimethyl, benzoyl, formyl radical, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl.
4) R
4, R
5, R
6For independently being hydrogen separately, hydroxyl, methoxyl group, ethoxy ethoxy, acetoxyl group, methanoyl, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6Form methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6Be hydrogen or hydroxyl, and have at least one not to be hydrogen.
Cicada slough amine B of the present invention, for the end at cicada slough amine A condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 2 two kinds of skeleton structures:
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein.
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein.
3) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene.
4) R
3, R
3' be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl.
5) R
4, R
5, R
6, R
6' for independently being hydrogen separately, hydroxyl, methoxyl group, acetoxyl group, ethoxy ethoxy, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6' the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6' be hydrogen or hydroxyl, and have at least one not to be hydrogen.
Cicada slough amine C of the present invention, for the end at cicada slough amine B condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 34 kinds of skeleton structures:
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein.
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein.
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum.
4) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene.
5) R
3, R
3', R
3" be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3; 4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3; 4-dimethoxy phenylacetyl, 3; 4; 5-trihydroxybenzene ethanoyl, 3-methoxyl group-4; 5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl.
6) R
4, R
5, R
6, R
6', R
6" for independently being hydrogen separately; hydroxyl; methoxyl group; acetoxyl group; ethoxy ethoxy; benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6" be hydrogen or hydroxyl, and have at least one not to be hydrogen.
Cicada slough amine D of the present invention, for the end at cicada slough amine C condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 48 kinds of skeleton structures:
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein.
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein.
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum.
4) 2 " ' position and 3 " ' absolute configuration can be respectively R or S configuration, wherein with 2 " ' R3 " ' S, 2 " ' S3 " ' R and 2 " ' R3 " ' R is optimum.
5) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene.
6) R
3, R
3', R
3", R
3" ' be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3; 4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3; 4-dimethoxy phenylacetyl, 3; 4; 5-trihydroxybenzene ethanoyl, 3-methoxyl group-4; 5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl.
7) R
4, R
5, R
6, R
6', R
6", R
6" ' for independently being hydrogen separately; hydroxyl; methoxyl group; acetoxyl group; ethoxy ethoxy; benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" ' the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6", R
6" ' be hydrogen or hydroxyl, and have at least one not to be hydrogen.
Cicada slough amine E of the present invention, for the end at cicada slough amine D condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 5 16 kinds of skeleton structures:
Structural formula 5
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein.
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein.
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum.
4) 2 " ' position and 3 " ' absolute configuration can be respectively R or S configuration, wherein with 2 " ' R3 " ' S, 2 " ' S3 " ' R and 2 " ' R3 " ' R is optimum.
5) 2 " " position and 3 " " absolute configuration can be respectively R or S configuration, wherein with 2 " " R3 " " S, 2 " " S3 " " R and 2 " " R3 " " R is optimum.
6) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene.
7) R
3, R
3', R
3", R
3" ', R
3" " be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl.
8) R
4, R
5, R
6, R
6', R
6", R
6" ', R
6" " for independently being hydrogen separately, hydroxyl, methoxyl group, acetoxyl group, ethoxy ethoxy, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" " the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6", R
6" ', R
6" " be hydrogen or hydroxyl, and have at least one not to be hydrogen.
Cicada slough amine F of the present invention condenses an acetyldopamine for the end at cicada slough amine E with the dioxane form; Cicada slough amine G condenses an acetyldopamine for the end at cicada slough amine F with the dioxane form; Cicada slough amine H condenses an acetyldopamine for the end at cicada slough amine G with the dioxane form; Cicada slough amine I condenses an acetyldopamine for the end at cicada slough amine H with the dioxane form; Cicada slough amine J condenses an acetyldopamine for the end at cicada slough amine I with the dioxane form; Cicada slough amine K condenses an acetyldopamine for the end at cicada slough amine J with the dioxane form.It condenses mode and substituting group type such as cicada slough amine E and condenses an acetyldopamine for the end at cicada slough amine D with the dioxane form.
Preferably, particular compound 1-compound 64 of the present invention etc. is as shown in table 1:
The chemical structure of table 1 compound 1-compound 64
Another object of the present invention is to provide and contains above-mentioned any one compound compositions.
Composition of the present invention can be prepared into: medicine, functional food, healthcare products and food.
Composition of the present invention is made up of any one compound and acceptable carrier among the above-mentioned cicada slough amine A-cicada slough amine K.
Any one compound is as pharmaceutically active substance among the cicada slough amine A-cicada slough amine K of the present invention, its shared weight percent in preparation can be 0.1-99.9%, all the other are the medicine acceptable carrier, and described medicine acceptable carrier shared weight percent in preparation is 0.1-99.9%.Pharmaceutical composition of the present invention exists with unit dosage form, and described unit dosage form is meant the unit of preparation, as every of tablet, and capsular every capsules, every bottle of oral liquid, every bag of granule etc.
Chinese medicine composition of the present invention can be any pharmaceutically useful formulation, and these formulations comprise: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, paste, sublimed preparation, suspensoid, pulvis, solution, injection, suppository, ointment, plaster, creme, sprays, drops, patch.Preparation of the present invention, oral dosage form preferably, as: capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, paste etc.
Composition of the present invention, the preparation of its oral administration can contain vehicle commonly used, such as tackiness agent, weighting agent, thinner, tablet agent, lubricant, disintegrating agent, tinting material, seasonings and wetting agent, can carry out dressing to tablet in case of necessity.
The weighting agent that is suitable for comprises Mierocrystalline cellulose, mannitol, lactose and other similar weighting agent.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivative, for example sodium starch glycollate.Suitable lubricant comprises, for example Magnesium Stearate.The acceptable wetting agent of appropriate drug comprises sodium lauryl sulphate.
Can fill by mixing, the method that compressing tablet etc. are commonly used prepares solid oral composition.Mix repeatedly active substance is distributed in those compositions of a large amount of weighting agents of whole use.
The form of oral liquid for example can be water-based or oily suspensions, solution, emulsion, syrup or elixir, perhaps can be a kind of used water before use or other suitable composite drying products of carrier.This liquid preparation can contain conventional additive, such as suspension agent, for example sorbyl alcohol, syrup, methylcellulose gum, gelatin, Natvosol, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible-fat, emulsifying agent, for example Yelkin TTS, anhydro sorbitol monooleate or gum arabic; Non-aqueous carrier (they can comprise edible oil), for example Prunus amygdalus oil, fractionated coconut oil, such as oily ester, propylene glycol or the ethanol of the ester of glycerine; Sanitas, for example para hydroxybenzene methyl esters or propylparaben or Sorbic Acid, and if desired, can contain conventional flavouring agent or tinting material.
For injection, the liquid unit dosage of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this compound can be suspended or dissolving.The preparation of solution is normally by being dissolved in active substance in a kind of carrier filter-sterilized before it is packed into a kind of suitable bottle or ampoule, sealing then.For example a kind of local anesthetic of auxiliary material, sanitas and buffer reagent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this composition is freezing, and under vacuum, water is removed.
Composition of the present invention, when being prepared into medicament, optionally add suitable medicine acceptable carrier (various solid preparations, liquid preparation, gel preparation, sustained-release preparation etc.), described medicine acceptable carrier is selected from: N.F,USP MANNITOL, sorbyl alcohol, Sodium Pyrosulfite, sodium bisulfite, Sulfothiorine, cysteine hydrochloride, Thiovanic acid, methionine(Met), vitamins C, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphoric acid salt or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium-chlor, Repone K, Sodium.alpha.-hydroxypropionate, Xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, Mierocrystalline cellulose and derivative thereof, alginate, gelatin, polyvinylpyrrolidone, glycerine, soil temperature 80, agar, lime carbonate, Calcium hydrogen carbonate, tensio-active agent, polyoxyethylene glycol, cyclodextrin, beta-cyclodextrin, the phospholipid material, kaolin, talcum powder, calcium stearate, Magnesium Stearate etc.
Pharmaceutical composition of the present invention is determined usage and dosage according to patient's situation in use, but obeys every day three times, each 1-20 agent, as: 1-20 bag or grain or sheet, every dose of 0.1mg-10.0g.
Another object of the present invention is to provide the pharmaceutical usage of compound of the present invention.
Dopamine HCL polymer in the cicada slough of the present invention and its derivative can be used for preparation treatment Parkinson's disease, anticonvulsion, nervous headache, dizzy, nerve degenerative diseases, nameless high-fever disappears, analgesic, antianaphylaxis, anti-allergic, analgesia, rubella, itch, the hot eyes ocular, convulsion with spasms, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, the pharyngalgia hoarsen, the hot eyes ocular, itch, protect the liver, transfer blood fat, hypoglycemic, promote gastric secretion, appetite stimulator, improve digestive function, antitumor, immunostimulant, antioxygenation, antidotal medicine, functional food, healthcare products and Application in Food.
Another object of the present invention is to provide the preparation method of compound of the present invention.
Preparation method of the present invention may further comprise the steps:
The organic solvent extraction of cicada slough water or different concns, the extracting solution concentrating under reduced pressure, make aqueous solution suspension, extract with sherwood oil, chloroform, ethyl acetate respectively, chloroform extract, be total cicada slough aminated compounds crude extract, continuing to separate with means such as silica gel column chromatography, polymeric amide, Sephadex LH-20 and HPLC obtains above compound.
Wherein organic solvent comprises ethanol, methyl alcohol, acetone, and optimum is 95% ethanol.During silica gel column chromatography, with low polar solvent elder generation wash-out decon, promptly obtain total diterpene ortho ester compounds with high polar solvent wash-out, wherein, low polar solvent can be chloroform, different ratios sherwood oil-acetone, different ratios petroleum ether-ethyl acetate, different ratios chloroform-methanol etc.; High polar solvent can be methyl alcohol, different ratios sherwood oil-acetone, different ratios petroleum ether-ethyl acetate, different ratios chloroform-methanol.Polyamide column chromatography, Sephadex LH-20 column chromatography, preparation property HPLC column chromatography can adopt a certain proportion of methanol-water or acetonitrile-water wash-out (electing the methanol-water wash-out of any concentration between the 10%-70% again as), perhaps methanol-water or acetonitrile-water gradient elution (electing the methanol-water gradient elution of 10%-70% again as) are collected purification of samples according to each chromatographic peak.More than, preparation process all can adopt high performance liquid chromatography-UV, visible light diode-array detector (HPLC-PDA), high performance liquid chromatography-mass spectrometry (HPLC-MS), Ultra Performance Liquid Chromatography-flight time mass spectrum coupling (UPLC-TOF-MS) to follow the tracks of and detect directed separating effective ingredient.And above 8 class phenylacetyl quinic acid and ester compounds thereof have been prepared with synthesizing mean.
Preferably, the preparation method of compound of the present invention may further comprise the steps:
Cicada slough medicinal material (perhaps full worm of any insect of Cicadidae or epidermis, cast off a skin), 95% ethanol of doubly measuring with medicinal material amount 4-10,70% second alcohol and water refluxing extraction are 2-4 time respectively, each 1-3h, after the extracting solution concentrating under reduced pressure is removed alcohol, merge, make the suspension of water, be total Dopamine HCL polymer crude extract; Use sherwood oil, chloroform, ethyl acetate extraction respectively 2-4 time, reclaim acetic acid ethyl ester extract, be the refining extract of total Dopamine HCL polymer.
Get acetic acid ethyl ester extract, (the solvent elution condition optimization is chloroform-methanol 100: 4-100: any concentration between 20) to utilize repeatedly silica gel column chromatography, (the solvent elution condition optimization is alcohol-water 5: 100-99 to polyamide column chromatography: any concentration between 1), (the solvent elution condition optimization is alcohol-water 5: 100-99 to Sephadex LH-20 column chromatography: any concentration between 1), and preparation property HPLC column chromatography can adopt a certain proportion of methanol-water or acetonitrile-water wash-out (being preferably the methanol-water wash-out of any concentration between the 10%-70%), perhaps methanol-water or acetonitrile-water gradient elution (being preferably the methanol-water gradient elution of 10%-70%) separate obtaining cicada slough amine A-cicada slough H series derivates.
Further preferred, the preparation method of compound of the present invention may further comprise the steps:
Cicada slough medicinal material (perhaps full worm of any insect of Cicadidae or epidermis, cast off a skin), 95% ethanol of doubly measuring with medicinal material amount 8-10,70% second alcohol and water refluxing extraction are three times respectively, each 2h, after the extracting solution concentrating under reduced pressure is removed alcohol, merge, make the suspension of water, be total Dopamine HCL polymer extract; Use sherwood oil, chloroform, ethyl acetate extraction respectively three times, reclaim acetic acid ethyl ester extract, be the refining extract of total Dopamine HCL polymer.
Get acetic acid ethyl ester extract, (the solvent elution condition optimization is chloroform-methanol 100: 4-100: any concentration between 20) to utilize repeatedly silica gel column chromatography, (the solvent elution condition optimization is alcohol-water 5: 100-99 to polyamide column chromatography: any concentration between 1), (the solvent elution condition optimization is alcohol-water 5: 100-99 to Sephadex LH-20 column chromatography: any concentration between 1), and preparation property HPLC column chromatography can adopt a certain proportion of methanol-water or acetonitrile-water wash-out (being preferably the methanol-water wash-out of any concentration between the 10%-70%), perhaps methanol-water or acetonitrile-water gradient elution (being preferably the methanol-water gradient elution of 10%-70%) separate obtaining cicada slough amine A-cicada slough H series derivates.
Optimum separation condition is as follows:
Get cicada slough medicinal material 5Kg, 10 times of amounts, 95% alcohol reflux three times each 3 hours, decompression and solvent recovery is concentrated into medicinal extract, gets medicinal extract 76g, and 6g keeps sample.Medicinal extract 70g silica gel column chromatography separates, and chloroform-methanol (100: 4,100: 5,100: 8,100: 10,100: 15) gradient elution.
The 97-108 flow point of chloroform-methanol (100: 5) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 30% part is again through preparation liquid phase 32%MeOH/H
2O gets compound 1 (360.6mg), compound 2 (322.4mg), through ODS column chromatography MeOH/H
2O gradient elution 40% part is again through preparation liquid phase 32%MeOH/H
2O compound 3 (7.5mg), compound 6 (21.3mg), compound 7 (19.5mg), compound 9 (13.1mg).
The 116-126 flow point of chloroform-methanol (100: 8) gradient elution merges, and carries out ODS column chromatography MeOH/H
2O gradient elution 30% part is again through preparation liquid phase 28%MeOH/H
2O gets compound 4 (40.8mg), compound 5 (30.9mg), ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 40%MeOH/H
2O gets compound 10 (40mg), compound 11 (40.6mg), compound 12 (11.0mg), compound 13 (159.3mg), compound 17 (13mg), compound 18 (14.0mg).
The 127-146 of chloroform-methanol (100: 8) gradient elution carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution, 60% part flow point merges, again through ODS column chromatography MeOH/H
2O gradient elution 45%-50% partly merges, through preparation liquid phase 38%MeOH/H
2O separates, and gets compound 19 (40mg), compound 20 (20.8mg).
The 147-165 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 8 (4.6mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 14 (25.0mg), compound 15 (35.5mg), compound 16 (13.1mg).ODS column chromatography 45% MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 21 (35.1mg), compound 22 (23.2mg), compound 23 (55.1mg), compound 24 (31.1mg), compound 25 (31.5mg), compound 26 (53.3mg).
The 166-195 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 40% part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 27 (35.1mg), compound 28 (23.2mg), compound 29 (55.1mg), compound 30 (31.1mg), compound 31 (31.5mg), compound 32 (53.3mg).ODS column chromatography MeOH/H
2O gradient elution 45% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 33 (25.0mg), compound 34 (35.5mg), compound 35 (13.1mg), compound 36 (35.1mg), compound 37 (23.2mg), compound 38 (55.1mg), compound 39 (31.1mg), compound 40 (31.5mg), compound 41 (53.3mg).ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 42 (25.0mg), compound 43 (35.5mg), compound 44 (13.1mg), compound 45 (35.1mg), compound 46 (23.2mg), compound 47 (55.1mg), compound 48 (31.1mg), compound 49 (31.5mg), compound 50 (53.3mg), compound 51 (31.5mg), compound 52 (53.3mg).
The 210-278 flow point of chloroform-methanol (100: 15) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 53 (35.5mg), compound 54 (13.1mg), compound 55 (35.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 56 (23.2mg), compound 57 (55.1mg), compound 58 (31.1mg), compound 59 (31.5mg).ODS column chromatography 45% MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 60 (53.3mg), compound 61 (31.5mg).
New compound of the present invention, through bioactivity research, find that Dopamine HCL polymer and the discovery of its derivative in the cicada slough of the present invention can be used for treating Parkinson's disease, anticonvulsion, nervous headache, dizzy, nerve degenerative diseases, nameless high-fever disappears, analgesic, antianaphylaxis, anti-allergic, analgesia, rubella, itch, the hot eyes ocular, convulsion with spasms, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, the pharyngalgia hoarsen, the hot eyes ocular, itch, protect the liver, transfer blood fat, hypoglycemic, promote gastric secretion, appetite stimulator, improve digestive function, antitumor, immunostimulant, antioxygenation, the anti-ageing effect of waiting for a long time is the basic substance of cicada slough performance pharmacological action.
Utilize HPLC-MS to analyze and proof (measuring method is as described below), in cicada, also contain the above composition of different content, illustrate that it also is the main effective constituent of cicada.Measurement result sees the following form:
(1) the grasshopper cicada belongs to Cryptotympana St (a)
A) yellow grasshopper cicada (Chinese name: south China grasshopper cicada) Cryptotympana mandarina Distant.
B) black grasshopper (has another name called: the grasshopper cicada) Cryptotympana pustulata Fabricius
C) mountain cicada Cicada flammata Dist.
(2) a kind of cicadahun belongs to Platypleura Amyot et Serville
A kind of cicadahun Platypleura kaempferi Fabricius
(3) the sandfly mqb belongs to Pycna Amyot et Serville
(4) net wing cicada belongs to Polyneura Westwood
Table 2
(5) the dung beetle cicada belongs to Pomponia St (a) l
(6) cicada in cold weather belongs to Meimuna Distant
(7) the spot cicada belongs to Gaeana Amyot et Serville
(8) the tiger spot cicada belongs to BecquartinaKato
(9) the blood-shot eye illness cicada belongs to Talainga Distant
(10) careless cicada belongs to Mogannia Amyot et Serville
(11) red cicada belongs to Huechys Amyot et Serville
(12) ring cicada Oncotympana maculaticollis Motschulsky
Table 3
The present invention also comprises the analytical procedure of compound of the present invention: analyzing as HPLC, is detector with mass spectrum (MS) detection, ultraviolet (UV) detection, circular dichroism spectrum (CD) detection, light scattering detector etc.
The configuration of reference substance solution: get Dopamine HCL polymer and its derivatives chemical reference substance precision and take by weighing in right amount, be mixed with an amount of reference substance solution with methyl alcohol.
The configuration of sample solution: precision takes by weighing the cicada slough sample, and each is an amount of, with methyl alcohol (or chloroform, ethyl acetate, acetone, acetonitrile, sherwood oil, organic solvent and solution in different concentration thereof such as hexanaphthene) extract, reclaim extracting solution, methyl alcohol (or chloroform, ethyl acetate, acetone, acetonitrile, sherwood oil, organic solvent and solution in different concentration thereof such as hexanaphthene) dissolving, the little chromatographic column pre-treatment of SPE through filling ODS (dodecyl bonded silica gel), water (perhaps lower concentration organic solvent) wash-out removal of impurities, continue with acetonitrile (or methyl alcohol, ethyl acetate, acetone, chloroform, sherwood oil, organic solvent and solution in different concentration thereof such as hexanaphthene) washing, merge elutriant, dissolve with methanol, constant volume, filter, promptly.
Testing method:
1) high performance liquid chromatography (HPLC) or Ultra Performance Liquid Chromatography (UPLC) method are measured the content of cicada slough aminated compounds in the cicada slough sample: carrying out the analyses of high performance liquid chromatography (HPLC) or Ultra Performance Liquid Chromatography (UPLC), is detector with mass spectrum (MS) detector, flight time mass spectrum (TOF-MS) detector, UV, visible light (UV) detector, UV, visible light diode-array detector, circular dichroism spectrum (CD) detector, light scattering detector etc.With the chromatographic peak area of each compound in the sample, corresponding chromatographic peak area with the standard control sample according to calibration curve method (or 1 method of external standard, 2 methods of external standard etc.), carries out quantitative analysis, calculates, promptly.
2) ultraviolet-visible spectrophotometry is measured the content of total cicada slough aminated compounds in the cicada slough sample: sample solution and reference substance solution, utilize ultraviolet-visible pectrophotometer, measure respectively absorbancy at the 245nm place, utilize formula: concentration (total cicada slough amine)=concentration (reference substance solution) * absorbancy (sample solution) * extension rate/absorbancy (sample solution) is calculated, that is the content of total cicada slough aminated compounds in the cicada slough sample.
Compound of the present invention is compared with the compound of existing similar structures, side effect still less, activity is stronger, stability is better, instant effect, dosage is few, has notable therapeutic effect.
Description of drawings
The leaching process of Fig. 1 The compounds of this invention
The extraction process of Fig. 2 The compounds of this invention
The sepn process of Fig. 3 The compounds of this invention
The UPLC of Fig. 4 cicada slough analyzes color atlas (with ODS is stationary phase, with methanol-water (containing methyl alcohol 0%-100%) gradient elution)
The HPLC_TOF-MS of Fig. 5 cicada slough analyzes color atlas (with ODS is stationary phase, with acetonitrile-water (containing acetonitrile 0%-100%) gradient elution)
Be respectively on to descending: the total ions chromatogram of ethanol extraction, Dopamine HCL dimer derivate are selected Li Ziliu color atlas ([M+H]
+M/z 387.152), the Dopamine HCL dimer derivate selects Li Ziliu color atlas ([M+H]
+M/z 425.097), Dopamine HCL tripolymer derivative selects Li Ziliu color atlas ([M+H]
+M/z 578.234), Dopamine HCL tetramer derivative selects Li Ziliu color atlas ([M+H]
+M/z 791.228), Dopamine HCL pentamer derivative selects Li Ziliu color atlas ([M+H]
+M/z984.297), Dopamine HCL pentamer derivative is selected Li Ziliu color atlas ([M+H]
+M/z 982.343)
The HPLC_TOF-MS of Fig. 6 cicada slough analyzes color atlas (with ODS is stationary phase, with acetonitrile-water (containing acetonitrile 0%-100%) gradient elution)
Be respectively on to descending: the total ions chromatogram of ethanol extraction, Dopamine HCL six aggressiveness derivatives are selected Li Ziliu color atlas ([M+H]
+M/z 1173.389), Dopamine HCL heptamer derivative selects Li Ziliu color atlas ([M+H]
+M/z 1366.460), Dopamine HCL heptamer derivative selects Li Ziliu color atlas ([M+2H]
2+M/z 679.391), Dopamine HCL eight aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z 777.415), Dopamine HCL nine aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z877.432), Dopamine HCL ten aggressiveness derivatives are selected Li Ziliu color atlas ([M+2H]
2+M/z 973.580)
The HPLC_TOF-MS of Fig. 7 cicada slough analyzes color atlas (with ODS is stationary phase, with acetonitrile-water (containing acetonitrile 0%-100%) gradient elution)
Be respectively on to descending: the total ions chromatogram of ethanol extraction, Dopamine HCL heptamer derivative are selected Li Ziliu color atlas ([M+2H]
2+M/z 679.391), Dopamine HCL eight aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z 777.415), Dopamine HCL nine aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z 877.432), Dopamine HCL ten aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z 973.580), Dopamine HCL 11 aggressiveness derivatives select Li Ziliu color atlas ([M+2H]
2+M/z 1064.675), Dopamine HCL ten dimer derivates select Li Ziliu color atlas ([M+2H]
2+M/z 1163.603)
Embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1: the extracting method of The compounds of this invention
The cicada slough medicinal material, use 95% ethanol, 70% second alcohol and water refluxing extraction three times respectively, each 2h, after the extracting solution concentrating under reduced pressure is removed alcohol, merge, make the suspension of water, use sherwood oil, chloroform, ethyl acetate extraction respectively three times, reclaim acetic acid ethyl ester extract, be total Dopamine HCL polymer extract.Leaching process is seen Fig. 1, and extraction process is seen Fig. 2.
Get acetic acid ethyl ester extract, utilize repeatedly means such as silica gel column chromatography, polymeric amide, Sephadex LH-20 and HPLC to separate and obtain cicada slough amine A-cicada slough H series derivates (structural formula is seen 1-5) altogether.Separation process is seen Fig. 3.
Wherein, the preparation method of particular compound and condition are as follows
Get cicada slough medicinal material 5Kg, 10 times of amounts, 95% alcohol reflux three times each 3 hours, decompression and solvent recovery is concentrated into medicinal extract, gets medicinal extract 76g, and 6g keeps sample.Medicinal extract 70g silica gel column chromatography separates, and chloroform-methanol (100: 4,100: 5,100: 8,100: 10,100: 15) gradient elution.
The 97-108 flow point of chloroform-methanol (100: 5) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 30% part is again through preparation liquid phase 32%MeOH/H
2O gets compound 1 (360.6mg), compound 2 (322.4mg), through ODS column chromatography MeOH/H
2O gradient elution 40% part is again through preparation liquid phase 32%MeOH/H
2O compound 3 (7.5mg), compound 6 (21.3mg), compound 7 (19.5mg), compound 9 (13.1mg).
The 116-126 flow point of chloroform-methanol (100: 8) gradient elution merges, and carries out ODS column chromatography MeOH/H
2O gradient elution 30% part is again through preparation liquid phase 28%MeOH/H
2O gets compound 4 (40.8mg), compound 5 (30.9mg), ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 40%MeOH/H
2O gets compound 10 (40mg), compound 11 (40.6mg), compound 12 (11.0mg), compound 13 (159.3mg), compound 17 (13mg), compound 18 (14.0mg).
The 127-146 of chloroform-methanol (100: 8) gradient elution carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution, 60% part flow point merges, again through ODS column chromatography MeOH/H
2O gradient elution 45%-50% partly merges, through preparation liquid phase 38%MeOH/H
2O separates, and gets compound 19 (40mg), compound 20 (20.8mg).
The 147-165 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 8 (4.6mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 14 (25.0mg), compound 15 (35.5mg), compound 16 (13.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 21 (35.1mg), compound 22 (23.2mg), compound 23 (55.1mg), compound 24 (31.1mg), compound 25 (31.5mg), compound 26 (53.3mg).
The 166-195 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 40% part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 27 (35.1mg), compound 28 (23.2mg), compound 29 (55.1mg), compound 30 (31.1mg), compound 31 (31.5mg), compound 32 (53.3mg).ODS column chromatography MeOH/H
2O gradient elution 45% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 33 (25.0mg), compound 34 (35.5mg), compound 35 (13.1mg), compound 36 (35.1mg), compound 37 (23.6mg), compound 38 (57.1mg), compound 39 (11.1mg), compound 40 (34.5mg), compound 41 (13.3mg).ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 42 (21.0mg), compound 43 (35.4mg), compound 44 (3.1mg), compound 45 (5.1mg), compound 46 (7.2mg), compound 47 (9.1mg), compound 48 (21.1mg), compound 49 (21.5mg), compound 50 (23.3mg), compound 51 (21.5mg), compound 52 (12.3mg).
The 210-278 flow point of chloroform-methanol (100: 15) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 53 (15.5mg), compound 54 (12.1mg), compound 55 (15.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 56 (21.2mg), compound 57 (15.1mg), compound 58 (21.2mg), compound 59 (11.2mg), compound 60 (13.1mg), compound 61 (11.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 62 (12.5mg), compound 63 (11.9mg), compound 64 (17.0mg).
The compound 1-compound 64 that separates preparation, all by 1HNMR, 13CNMR, UV, IR, TOF-MS, HMBC, HSQC,
1H-
1HCOSY etc. determine that its chemical structure is as shown in table 1.
Embodiment 2: qualitative, the quantitative analysis of cicada slough aminated compounds
The configuration of reference substance solution: get Dopamine HCL polymer and its derivatives chemical reference substance precision and take by weighing in right amount, be mixed with an amount of reference substance solution with methyl alcohol.
The configuration of sample solution: precision takes by weighing the about 1g of system cicada slough powder, put in the tool plug triangular flask, the accurate ethanol 25mL that adds, the accurate title, decided quality, supersound process 0.5h under the room temperature, taking-up is cooled to room temperature, supply the quality of minimizing with 70% methyl alcohol, leave standstill after shaking up, it is centrifugal to get supernatant liquor, get after centrifugal in supernatant liquor 5ml to the 50ml volumetric flask, water is settled to scale, shakes up, and gets 10ml and goes up through pretreated ODS-SPE pillar, washing 10ml earlier with water discards, continue with about 5ml to the 5ml volumetric flask of 50%MeOH wash-out, 50%MeOH is settled to scale, after shaking up, cross 0.22 μ m filter membrane, be need testing solution.
Testing method: carry out the analyses of high performance liquid chromatography (HPLC) or Ultra Performance Liquid Chromatography (UPLC), with ODS is stationary phase, with methanol-water (containing methyl alcohol 0%-100%) or acetonitrile-water (containing acetonitrile 0%-100%) gradient elution, be detector with mass spectrum (MS) detector, flight time mass spectrum (TOF-MS) detector, UV, visible light (UV) detector, UV, visible light diode-array detector, circular dichroism spectrum (CD) detector, light scattering detector etc.With the chromatographic peak area of each compound in the sample, corresponding chromatographic peak area with the standard control sample according to calibration curve method (or 1 method of external standard, 2 methods of external standard etc.), carries out quantitative analysis, calculates, promptly.
The stratographic analysis result: figure below is the color atlas of part experiment test.See Fig. 4-7.
Embodiment 3: preparation of drug combination
Any one compound of the present invention and medicine acceptable carrier, or with the other drug compatibility, mix to be prepared into tablet with the technology of pharmaceutics routine techniques, capsule, particle, oral liquid, preparations such as injection.
Embodiment 4:
Effective constituent is as Yuanhuadine in the prior art, chlorogenic acid, the panaxan, Radix Ginseng total saponinss etc. and Dopamine HCL polymer of the present invention and its derivative are treated Parkinson's disease, anticonvulsion, nervous headache, dizzy, convulsion with spasms, nerve degenerative diseases, nameless high-fever disappears, analgesic, analgesia, antianaphylaxis, anti-allergic, rubella, itch, the hot eyes ocular, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, the pharyngalgia hoarsen, the hot eyes ocular, itch, protect the liver, antitumor, transfer blood fat, hypoglycemic, promote gastric secretion, appetite stimulator, improve digestive function, immunostimulant, antioxygenation, anti-ageing wait for a long time pharmacology and toxicity comparison.The compounds of this invention is better than the prior art compound as a result.
The data such as the following table of its treatment Parkinson's disease, anticonvulsion, convulsion with spasms, nervous headache, the effective constituent that performance treatment Parkinson's disease, anticonvulsion, convulsion with spasms, nervous headache effect are described in the cicada slough is Dopamine HCL polymer and its derivative of The compounds of this invention, and wherein The compounds of this invention is stronger than known compound Dopamine HCL activity:
Table 4
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 15 |
| Cicada slough amine G1 | 10 |
| Cicada slough amine H1 | 5 |
| Cicada slough amine I 1 | 5 |
| Cicada slough amine J 1 | 15 |
| Cicada slough amine K 1 | 15 |
| Total cicada slough amine extract | 30 |
| Dopamine HCL | 50 |
The data such as the following table of its treatment nerve degenerative diseases, the effective constituent that performance nerve degenerative diseases in the cicada slough is described is Dopamine HCL polymer and its derivative of The compounds of this invention, wherein The compounds of this invention is stronger than known compound ginsenoside Rg1 activity:
Table 5
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F2 | 15 |
| Cicada slough amine G2 | 20 |
| Cicada slough amine H1 | 15 |
| Cicada slough amine I 1 | 15 |
| Cicada slough amine J 1 | 15 |
| Cicada slough amine K 1 | 15 |
| Total cicada slough amine extract | |
| The ginsenoside Rg1 | 200 |
Its nameless high-fever that disappears, analgesic, analgesic data such as following table, the Dopamine HCL polymer and its derivative that disappear performance nameless high-fever, effective constituent analgesic, analgesic activity be The compounds of this invention are described in the cicada slough, and wherein The compounds of this invention is stronger than known compound acetylsalicylic acid activity:
Table 6
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
20 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
20 |
| Cicada slough amine I 1 | 25 |
| Cicada |
15 |
| Cicada |
15 |
| Total cicada slough amine extract | 30 |
| |
100 |
The data of its antianaphylaxis, anti-allergic such as following table, illustrate that the effective constituent of bringing into play antianaphylaxis, anti-allergy action in the cicada slough is Dopamine HCL polymer and its derivative of The compounds of this invention, wherein The compounds of this invention is stronger than known compound Toldrin activity:
Table 7
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 10 |
| Cicada slough amine E1 | 15 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 15 |
| Cicada slough amine G1 | 20 |
| Cicada slough amine H2 | 20 |
| Cicada slough amine I 1 | 15 |
| Cicada slough amine J 1 | 15 |
| Cicada slough amine K 1 | 15 |
| Total cicada slough amine extract | 30 |
| Toldrin | 150 |
The data such as the following table of its treatment rubella, itch, hot eyes ocular, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, pharyngalgia hoarsen, hot eyes ocular, itch, illustrate that the effective constituent of bringing into play rubella, itch, hot eyes ocular, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, pharyngalgia hoarsen, hot eyes ocular, itch effect in the cicada slough is Dopamine HCL polymer and its derivative of The compounds of this invention, wherein The compounds of this invention and cicada slough crude extract are quite active:
Table 8
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 15 |
| Cicada slough amine G1 | 20 |
| Cicada slough amine H1 | 15 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 50 |
| Total cicada slough crude extract | 500 (mg/Kg body weight) |
The data of its antitumor action such as following table illustrate that antitumor effective constituent is Dopamine HCL polymer and its derivative of The compounds of this invention in the cicada slough, and wherein The compounds of this invention is stronger than known compound Yuanhuadine activity:
Table 9
The data such as the following table of its anti-hepatic fibrosis and protection liver injury; illustrate that the performance anti-hepatic fibrosis is Dopamine HCL polymer and its derivative of The compounds of this invention with the effective constituent of protecting the liver injury effect in the cicada slough, wherein The compounds of this invention is stronger than known compound chlorogenic acid activity:
Table 10
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 19 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 18 |
| Cicada slough amine G1 | 12 |
| Cicada slough amine H1 | 19 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| Chlorogenic acid | 120 |
Its hypoglycemic data such as following table, the effective constituent that performance hypoglycemic activity in the cicada slough is described are Dopamine HCL polymer and its derivative of The compounds of this invention, and wherein The compounds of this invention is quite more active than known compound N1,N1-Dimethylbiguanide, miglitol:
Table 11
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 5 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 5 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 10 |
| Cicada slough amine G1 | 15 |
| Cicada slough amine H1 | 10 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| N1,N1-Dimethylbiguanide | 10 |
| Miglitol | 50.0 |
Data such as following table that it transfers blood fat illustrate that the effective constituent of performance accent blood fat in the cicada slough is Dopamine HCL polymer and its derivative of The compounds of this invention, and wherein The compounds of this invention and known compound Fructus Crataegi extract are quite active:
Table 12
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 50 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine F1 | 10 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine G1 | 30 |
| Cicada slough amine H1 | 10 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| Fructus Crataegi extract | 80.0 |
The data of its immunostimulant such as following table, the effective constituent that performance immuno-potentiation in the cicada slough is described are Dopamine HCL polymer and its derivative of The compounds of this invention, and wherein The compounds of this invention is more active quite than known compound panaxan:
Table 13
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 10 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 10 |
| Cicada slough amine G1 | 10 |
| Cicada slough amine H1 | 40 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| The panaxan | 100.0 |
Its oxidation resistant data such as following table, the effective constituent that performance antioxygenation in the cicada slough is described is Dopamine HCL polymer and its derivative of The compounds of this invention, wherein The compounds of this invention is stronger than known compound chlorogenic acid activity:
Table 14
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 20 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 10 |
| Cicada slough amine G1 | 10 |
| Cicada slough amine H1 | 10 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| Chlorogenic acid | 100 |
It promotes gastric secretion, appetite stimulator, the data of improving digestive function such as following table, illustrates that effective constituent is Dopamine HCL polymer and its derivative in the cicada slough, and wherein The compounds of this invention and known compound Fructus Crataegi extract are quite active:
Table 15
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada slough amine B1 | 15 |
| Cicada slough amine B2 | 15 |
| Cicada slough amine B3 | 15 |
| Cicada slough amine B4 | 15 |
| Cicada slough amine B5 | 15 |
| Cicada slough amine B6 | 15 |
| Cicada slough amine B7 | 15 |
| Cicada slough amine B8 | 15 |
| Cicada slough amine B9 | 15 |
| Cicada slough amine B10 | 15 |
| Cicada slough amine C1 | 25 |
| Cicada slough amine C2 | 25 |
| Cicada slough amine C3 | 25 |
| Cicada slough amine C4 | 25 |
| Cicada slough amine C5 | 25 |
| Cicada slough amine C6 | 25 |
| Cicada slough amine C7 | 25 |
| Cicada slough amine C8 | 25 |
| Cicada slough amine C9 | 25 |
| Cicada slough amine C10 | 25 |
| Cicada slough amine D1 | 50 |
| Cicada slough amine D2 | 20 |
| Cicada slough amine D3 | 20 |
| Cicada slough amine D4 | 20 |
| Cicada slough amine D5 | 20 |
| Cicada slough amine D6 | 20 |
| Cicada slough amine D7 | 20 |
| Cicada slough amine D8 | 20 |
| Cicada slough amine E1 | 20 |
| Cicada slough amine E2 | 20 |
| Cicada slough amine E3 | 20 |
| Cicada slough amine E4 | 20 |
| Cicada slough amine E5 | 20 |
| Cicada slough amine E6 | 20 |
| Cicada slough amine E7 | 20 |
| Cicada slough amine E8 | 20 |
| Cicada slough amine E9 | 20 |
| Cicada slough amine E10 | 20 |
| Cicada slough amine E11 | 20 |
| Cicada slough amine E12 | 20 |
| Cicada slough amine E13 | 20 |
| Cicada slough amine E14 | 20 |
| Cicada slough amine E15 | 20 |
| Cicada slough amine E16 | 20 |
| Cicada slough amine F1 | 10 |
| Cicada slough amine G1 | 30 |
| Cicada slough amine H1 | 10 |
| Cicada slough amine I1 | 15 |
| Cicada slough amine J1 | 15 |
| Cicada slough amine K1 | 15 |
| Total cicada slough amine extract | 30 |
| Fructus Crataegi extract | 80 |
Its antidotal data such as following table, the effective constituent that performance anti-aging effects in the cicada slough is described is Dopamine HCL polymer and its derivative of The compounds of this invention, wherein The compounds of this invention is stronger than known compound Radix Ginseng total saponins Rg1 activity:
Table 16
| The compound title | Effective dose (mmol/Kg body weight) |
| Cicada slough amine A1 | 10 |
| Cicada slough amine A2 | 10 |
| Cicada slough amine A3 | 10 |
| Cicada slough amine A4 | 10 |
| Cicada slough amine A5 | 10 |
| Cicada slough amine A6 | 10 |
| Cicada slough amine A7 | 10 |
| Cicada slough amine A8 | 10 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
15 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
| Cicada |
25 |
Claims (12)
1. a class is passed through the compound that extraction separation obtains from cicada slough, described compound comprises cicada slough amine A and derivative thereof, cicada slough amine B and derivative thereof, cicada slough amine C and derivative thereof, cicada slough amine D and derivative thereof, cicada slough amine E and derivative thereof, cicada slough amine F and derivative thereof, cicada slough amine G and derivative thereof, cicada slough amine H and derivative thereof, cicada slough amine I and derivative thereof, cicada slough amine J and derivative thereof, with any one compound in cicada slough amine K and the derivative thereof, their structure exists with polymer form, and the latter is Duoed a polymer monomer than the former, as cicada slough amine A is the double focusing thing, cicada slough amine B is a trimer, and by that analogy, cicada slough amine K is 12 polymers, and, there is different substituting groups in classes of compounds, the polymeric position isomerism, polymeric is along (cis) anti-(trans) isomery, with various derivatives such as glucosides replacements, wherein cicada slough amine A and derivative thereof, structural formula is as follows:
Structural formula 1
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2R3R and 2S3S wherein,
2) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 1-amino-ethyl, the amino straight or branched alkyl that replaces; Wherein optimum is a hydrogen, the 2-amino-ethyl, and comprise: above substituent amino is by formylation, benzoylation, phenylacetylization, the para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, the acetylize of 4-hydroxy 3-methoxybenzene, 3, the acetylize of 4-dimethoxy benzene, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene,
3) R
3Be hydrogen, methyl, dimethyl, benzoyl, formyl radical, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl,
4) R
4, R
5, R
6For independently being hydrogen separately, hydroxyl, methoxyl group, ethoxy ethoxy, acetoxyl group, methanoyl, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6Form methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose, and wherein optimum is R
4, R
5, R
6Be hydrogen or hydroxyl, and have at least one not to be hydrogen.
2. compound according to claim 1 is characterized in that, wherein cicada slough amine B and derivative thereof, and for the end at cicada slough amine A condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 2 two kinds of skeleton structures:
Structural formula 2
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein,
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein,
3) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene,
4) R
3, R
3' be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl,
5) R
4, R
5, R
6, R
6' for independently being hydrogen separately, hydroxyl, methoxyl group, acetoxyl group, ethoxy ethoxy, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6' the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6' be hydrogen or hydroxyl, and have at least one not to be hydrogen.
3. compound according to claim 1 is characterized in that, wherein cicada slough amine C and derivative thereof, and for the end at cicada slough amine B condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 34 kinds of skeleton structures:
Structural formula 3
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein.
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein,
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum,
4) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene,
5) R
3, R
3', R
3" be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3; 4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3; 4-dimethoxy phenylacetyl, 3; 4; 5-trihydroxybenzene ethanoyl, 3-methoxyl group-4; 5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl,
6) R
4, R
5, R
6, R
6', R
6" for independently being hydrogen separately; hydroxyl; methoxyl group; acetoxyl group; ethoxy ethoxy; benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6" be hydrogen or hydroxyl, and have at least one not to be hydrogen.
4. compound according to claim 1 is characterized in that, wherein cicada slough amine D and derivative thereof, and for the end at cicada slough amine C condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 48 kinds of skeleton structures:
Structural formula 4
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein,
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein,
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum,
4) 2 " ' position and 3 " ' absolute configuration can be respectively R or S configuration, wherein with 2 " ' R3 " ' S, 2 " ' S3 " ' R and 2 " ' R3 " ' R is optimum,
5) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene,
6) R
3, R
3', R
3", R
3" ' be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3; 4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3; 4-dimethoxy phenylacetyl, 3; 4; 5-trihydroxybenzene ethanoyl, 3-methoxyl group-4; 5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl,
7) R
4, R
5, R
6, R
6', R
6", R
6" ' for independently being hydrogen separately; hydroxyl; methoxyl group; acetoxyl group; ethoxy ethoxy; benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" ' the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6", R
6" ' be hydrogen or hydroxyl, and have at least one not to be hydrogen.
5. compound according to claim 1 is characterized in that, wherein cicada slough amine E and derivative thereof, and for the end at cicada slough amine D condenses an acetyldopamine derivative with the dioxane form, it is one of any to have shown in the structural formula 5 16 kinds of skeleton structures:
Structural formula 5
Wherein:
1) 2 and 3 s' absolute configuration can be respectively R or S configuration, is optimum with 2R3S, 2S3R and 2R3R wherein,
2) 2 ' and 3 ' 's absolute configuration can be respectively R or S configuration, is optimum with 2 ' R3 ' S, 2 ' S3 ' R and 2 ' R3 ' R wherein,
3) 2 " position and 3 " absolute configuration can be respectively R or S configuration, wherein with 2 " R3 " S, 2 " S3 " R and 2 " R3 " R is optimum,
4) 2 " ' position and 3 " ' absolute configuration can be respectively R or S configuration, wherein with 2 " ' R3 " ' S, 2 " ' S3 " ' R and 2 " ' R3 " ' R is optimum,
5) 2 " " position and 3 " " absolute configuration can be respectively R or S configuration, wherein with 2 " " R3 " " S, 2 " " S3 " " R and 2 " " R3 " " R is optimum,
6) R
1, R
2For separately independently hydrogen, hydroxyl, amino, aminomethyl, 2-amino-ethyl, 2-amido vinyl, 2-glycyl, carbamoyl methyl, 1-hydroxyl-2-amino-ethyl, 1-amino-ethyl, 2-hydroxyl-1-amino-ethyl, the amino straight or branched alkyl that replaces, the amino straight or branched thiazolinyl that replaces, the amino saturated or undersaturated straight or branched acyl group that replaces; Wherein optimum is hydrogen, 2-amino-ethyl, 2-amido vinyl.And comprise, more than substituent amino by benzoylation, phenylacetylization, para hydroxybenzene acetylize, acetanisoleization, 3, the acetylize of 4-dihydroxy-benzene, 3-hydroxyl-4-anisole acetylize, 4-hydroxy 3-methoxybenzene acetylize, 3,4-dimethoxy benzene acetylize, 3,4, the acetylize of 5-trihydroxybenzene, 3-methoxyl group-4, the acetylize of 5-dihydroxy-benzene, 4-methoxyl group-3, the acetylize of 5-dihydroxy-benzene, 3-hydroxyl-4, the acetylize of 5-dimethoxy benzene, 4-hydroxyl-3,5-dimethoxy benzene acetylize or 3,4, the acetylize of 5-trimethoxy-benzene; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize, benzoylation or 3, the acetylize of 4-dihydroxy-benzene,
7) R
3, R
3', R
3", R
3" ', R
3" " be hydrogen, methyl, dimethyl, ethanoyl, benzoyl, phenylacetyl, para hydroxybenzene ethanoyl, acetanisole base, 3,4-dihydroxy-benzene ethanoyl, 3-hydroxyl-4-anisole ethanoyl, 4-hydroxy 3-methoxybenzene ethanoyl, 3,4-dimethoxy phenylacetyl, 3,4,5-trihydroxybenzene ethanoyl, 3-methoxyl group-4,5-dihydroxy-benzene ethanoyl, 4-methoxyl group-3,5-dihydroxy-benzene ethanoyl, 3-hydroxyl-4,5-dimethoxy phenylacetyl, 4-hydroxyl-3,5-dimethoxy phenylacetyl or 3,4,5-trimethoxy phenylacetyl; Wherein optimum is ethanoyl, hydrogen, para hydroxybenzene acetylize or 3,4-dihydroxy-benzene ethanoyl,
8) R
4, R
5, R
6, R
6', R
6", R
6" ', R
6" " for independently being hydrogen separately, hydroxyl, methoxyl group, acetoxyl group, ethoxy ethoxy, benzoyloxy, phenylacetyl oxygen base, the para hydroxybenzene acetoxyl group, acetanisole oxygen base, 3,4-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4-anisole acetoxyl group, 4-hydroxy 3-methoxybenzene acetoxyl group, 3,4-dimethoxy benzene acetoxyl group, 3,4,5-trihydroxybenzene acetoxyl group, 3-methoxyl group-4,5-dihydroxy-benzene acetoxyl group, 4-methoxyl group-3,5-dihydroxy-benzene acetoxyl group, 3-hydroxyl-4,5-dimethoxy benzene acetoxyl group, 4-hydroxyl-3,5-dimethoxy benzene acetoxyl group or 3,4,5-trimethoxy-benzene acetoxyl group; Perhaps R
4Respectively with R
5, R
6" " the formation methylene-dioxy; Hydroxyl in the perhaps above compound is glucose, wood sugar, pectinose, rhamnosyl, seminose, rock algae disaccharide, rutinose etc.Wherein optimum is R
4, R
5, R
6, R
6", R
6" ', R
6" " be hydrogen or hydroxyl, and have at least one not to be hydrogen.
6. compound according to claim 1 is characterized in that, wherein: cicada slough amine F and derivative thereof condense an acetyldopamine for the end at cicada slough amine E and derivative thereof with the dioxane form; Cicada slough amine G and derivative thereof condense an acetyldopamine for the end at cicada slough amine F and derivative thereof with the dioxane form; Cicada slough amine H and derivative thereof condense an acetyldopamine for the end at cicada slough amine G and derivative thereof with the dioxane form; Cicada slough amine I and derivative thereof condense an acetyldopamine for the end at cicada slough amine H and derivative thereof with the dioxane form; Cicada slough amine J and derivative thereof condense an acetyldopamine for the end at cicada slough amine I and derivative thereof with the dioxane form; Cicada slough amine K and derivative thereof condense an acetyldopamine for the end at cicada slough amine J and derivative thereof with the dioxane form; Cicada slough amine E is for condensing the situation of an acetyldopamine in the mode that condenses of above classes of compounds and substituting group type such as the claim 5 with the dioxane form at the end of cicada slough amine D.
7. compound according to claim 1 is characterized in that having the described chemical structure of following table.
8. the compound of any one is treated Parkinson's disease in preparation among the claim 1-7, anticonvulsion, nervous headache, dizzy, nerve degenerative diseases, nameless high-fever disappears, analgesic, antianaphylaxis, anti-allergic, analgesia, rubella, itch, the hot eyes ocular, convulsion with spasms, tetanus, common cold due to wind-heat, cough, measles without adequate eruption, the pharyngalgia hoarsen, the hot eyes ocular, itch, protect the liver, transfer blood fat, hypoglycemic, promote gastric secretion, appetite stimulator, improve digestive function, antitumor, immunostimulant, antioxygenation, antidotal medicine, functional food, healthcare products and Application in Food.
9. the pharmaceutical composition that contains any one compound among the claim 1-7.
10. the preparation method of any one compound among the claim 1-7 may further comprise the steps:
The organic solvent extraction of cicada slough (perhaps full worm of any insect of Cicadidae or epidermis, cast off a skin) water or different concns, the extracting solution concentrating under reduced pressure, make aqueous solution suspension, be total cicada slough aminated compounds crude extract, total cicada slough aminated compounds crude extract extracts with sherwood oil, chloroform, ethyl acetate respectively, chloroform extract is the refining extract of total cicada slough aminated compounds.The refining extract of total cicada slough aminated compounds continues can separate with means such as silica gel column chromatography, polymeric amide, Sephadex LH-20 and HPLC and obtains above compound, and wherein organic solvent comprises ethanol, methyl alcohol, acetone, and optimum is 95% ethanol.
During silica gel column chromatography, with low polar solvent elder generation wash-out decon, promptly obtain total diterpene ortho ester compounds with high polar solvent wash-out, wherein, low polar solvent can be chloroform, different ratios sherwood oil-acetone, different ratios petroleum ether-ethyl acetate, different ratios chloroform-methanol etc.; High polar solvent can be methyl alcohol, different ratios sherwood oil-acetone, different ratios petroleum ether-ethyl acetate, different ratios chloroform-methanol; The solvent elution condition optimization is chloroform-methanol 100: 4-100: any concentration gradient wash-out between 20.Polyamide column chromatography, Sephadex LH-20 column chromatography, preparation property HPLC column chromatography can adopt a certain proportion of methanol-water or acetonitrile-water wash-out (being preferably the methanol-water wash-out of any concentration between the 10%-70%), perhaps methanol-water or acetonitrile-water gradient elution (being preferably the methanol-water gradient elution of 10%-70%), collect purification of samples according to each chromatographic peak, more than, preparation process all can adopt high performance liquid chromatography-UV, visible light diode-array detector (HPLC-PDA), high performance liquid chromatography-mass spectrometry (HPLC-MS), Ultra Performance Liquid Chromatography-flight time mass spectrum coupling (UPLC-TOF-MS) is followed the tracks of and is detected, directed separating effective ingredient, or carry out the control of cicada slough and Products Quality thereof
Content assaying method wherein is as follows:
1) high performance liquid chromatography (HPLC) or Ultra Performance Liquid Chromatography (UPLC) method are measured the content of cicada slough aminated compounds in the cicada slough sample: carrying out the analyses of high performance liquid chromatography (HPLC) or Ultra Performance Liquid Chromatography (UPLC), is detector with mass spectrum (MS) detector, flight time mass spectrum (TOF-MS) detector, UV, visible light (UV) detector, UV, visible light diode-array detector, circular dichroism spectrum (CD) detector, light scattering detector etc.With the chromatographic peak area of each compound in the sample, corresponding chromatographic peak area with the standard control sample according to calibration curve method (or 1 method of external standard, 2 methods of external standard etc.), carries out quantitative analysis, calculates, promptly;
2) ultraviolet-visible spectrophotometry is measured the content of total cicada slough aminated compounds in the cicada slough sample: sample solution and reference substance solution, utilize ultraviolet-visible pectrophotometer, measure respectively absorbancy at the 245nm place, utilize formula: concentration (total cicada slough amine)=concentration (reference substance solution) * absorbancy (sample solution) * extension rate/absorbancy (sample solution) is calculated, that is the content of total cicada slough aminated compounds in the cicada slough sample.
11. preparation method according to claim 10 is characterized in that, may further comprise the steps:
Cicada slough medicinal material (perhaps full worm of any insect of Cicadidae or epidermis, cast off a skin) is used 95% ethanol, 70% second alcohol and water refluxing extraction three times respectively, each 2h, after the extracting solution concentrating under reduced pressure is removed alcohol, merge, make the suspension of water, be total Dopamine HCL polymer extract; Also can be further by using sherwood oil, chloroform, ethyl acetate extraction respectively three times, reclaim acetic acid ethyl ester extract, be the refining extract of total Dopamine HCL polymer extract;
Get acetic acid ethyl ester extract, (the solvent elution condition optimization is chloroform-methanol 100: 4-100: any concentration between 20) to utilize repeatedly silica gel column chromatography, (the solvent elution condition optimization is alcohol-water 5: 100-99 to polyamide column chromatography: any concentration between 1), (the solvent elution condition optimization is alcohol-water 5: 100-99 to Sephadex LH-20 column chromatography: any concentration between 1), and preparation property HPLC column chromatography can adopt a certain proportion of methanol-water or acetonitrile-water wash-out (being preferably the methanol-water wash-out of any concentration between the 10%-70%), perhaps methanol-water or acetonitrile-water gradient elution (being preferably the methanol-water gradient elution of 10%-70%) separate obtaining cicada slough amine A-cicada slough H series derivates.
12. preparation method according to claim 11 is characterized in that, wherein the concrete preparation method of particular compound 1-compound 64 is as follows:
Get cicada slough medicinal material 5Kg, 10 times of amounts, 95% alcohol reflux three times each 3 hours, decompression and solvent recovery is concentrated into medicinal extract, gets medicinal extract 76g, and 6g keeps sample.Medicinal extract 70g silica gel column chromatography separates, and chloroform-methanol (100: 4,100: 5,100: 8,100: 10,100: 15) gradient elution;
The 97-108 flow point of chloroform-methanol (100: 5) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 30% part is again through preparation liquid phase 32%MeOH/H
2O gets compound 1 (360.6mg), compound 2 (322.4mg), through ODS column chromatography MeOH/H
2O gradient elution 40% part is again through preparation liquid phase 32%MeOH/H
2O compound 3 (7.5mg), compound 6 (21.3mg), compound 7 (19.5mg), compound 9 (13.1mg);
The 116-126 flow point of chloroform-methanol (100: 8) gradient elution merges, and carries out ODS column chromatography MeOH/H
2O gradient elution 30% part is again through preparation liquid phase 28%MeOH/H
2O gets compound 4 (40.8mg), compound 5 (30.9mg), ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 40%MeOH/H
2O gets compound 10 (40mg), compound 11 (40.6mg), compound 12 (11.0mg), compound 13 (159.3mg), compound 17 (13mg), compound 18 (14.0mg);
The 127-146 of chloroform-methanol (100: 8) gradient elution carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution, 60% part flow point merges, again through ODS column chromatography MeOH/H
2O gradient elution 45%-50% partly merges, through preparation liquid phase 38%MeOH/H
2O separates, and gets compound 19 (40mg), compound 20 (20.8mg);
The 147-165 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 8 (4.6mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 14 (25.0mg), compound 15 (35.5mg), compound 16 (13.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 21 (35.1mg), compound 22 (23.2mg), compound 23 (55.1mg), compound 24 (31.1mg), compound 25 (31.5mg), compound 26 (53.3mg);
The 166-195 flow point of chloroform-methanol (100: 10) gradient elution merges, and carries out the ODS column chromatography, methanol (MeOH/H
2O) gradient elution 40% part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 27 (35.1mg), compound 28 (23.2mg), compound 29 (55.1mg), compound 30 (31.1mg), compound 31 (31.5mg), compound 32 (53.3mg).ODS column chromatography MeOH/H
2O gradient elution 45% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 33 (25.0mg), compound 34 (35.5mg), compound 35 (13.1mg), compound 36 (35.1mg), compound 37 (23.6mg), compound 38 (57.1mg), compound 39 (11.1mg), compound 40 (34.5mg), compound 41 (13.3mg).ODS column chromatography MeOH/H
2O gradient elution 50% part is again through preparation liquid phase 38%MeOH/H
2O gets compound 42 (21.0mg), compound 43 (35.4mg), compound 44 (3.1mg), compound 45 (5.1mg), compound 46 (7.2mg), compound 47 (9.1mg), compound 48 (21.1mg), compound 49 (21.5mg), compound 50 (23.3mg), compound 51 (21.5mg), compound 52 (12.3mg);
The 210-278 flow point of chloroform-methanol (100: 15) gradient elution merges, and carries out the ODS column chromatography, 40% methanol (MeOH/H
2O) gradient elution part is again through preparation liquid phase MeOH/H
2The O gradient elution gets compound 53 (15.5mg), compound 54 (12.1mg), compound 55 (15.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 56 (21.2mg), compound 57 (15.1mg), compound 58 (21.2mg), compound 59 (11.2mg), compound 60 (13.1mg), compound 61 (11.1mg).ODS column chromatography 45%MeOH/H
2O gradient elution part is again through preparation liquid phase 38%MeOH/H
2O gets compound 62 (12.5mg), compound 63 (11.9mg), compound 64 (17.0mg).
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| WO2018160021A1 (en) * | 2017-02-28 | 2018-09-07 | 한국 한의학 연구원 | Composition, containing oxya chinensis sinuosa extract or compound isolated therefrom as active ingredient, for prevention, relief, or treatment of skin wrinkles |
| CN110441459A (en) * | 2019-08-27 | 2019-11-12 | 江苏卫生健康职业学院 | The qualitative checking method of acetyldopamine in a kind of cicada slough |
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| CN110441459A (en) * | 2019-08-27 | 2019-11-12 | 江苏卫生健康职业学院 | The qualitative checking method of acetyldopamine in a kind of cicada slough |
| CN110464720A (en) * | 2019-08-27 | 2019-11-19 | 江苏省中医药研究院 | A kind of cicada slough acetyldopamine polymer composition and its application with prevention and treatment irritable bowel syndrome |
| CN110464720B (en) * | 2019-08-27 | 2022-06-28 | 天士力医药集团股份有限公司 | Periostracum cicada acetyl dopamine polymer composition for preventing and treating irritable bowel syndrome and application thereof |
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| CN110818585A (en) * | 2019-11-12 | 2020-02-21 | 遵义医科大学 | Separation method for simultaneously preparing five dopamine compounds from aspongopus |
| CN110818585B (en) * | 2019-11-12 | 2023-05-30 | 遵义医科大学 | Separation method for simultaneously preparing five dopamine compounds from aspongopus |
| CN113144142A (en) * | 2021-02-02 | 2021-07-23 | 深圳弘汇生物医药有限公司 | Traditional Chinese medicine composition for treating nephritis and medical application thereof |
| CN116554142A (en) * | 2023-05-11 | 2023-08-08 | 江苏省中医药研究院 | Periostracum cicada acetyl dopamine oligomer composition for treating allergic asthma |
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