CN106728671A - It is a kind of to treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof - Google Patents

It is a kind of to treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof Download PDF

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CN106728671A
CN106728671A CN201611134497.1A CN201611134497A CN106728671A CN 106728671 A CN106728671 A CN 106728671A CN 201611134497 A CN201611134497 A CN 201611134497A CN 106728671 A CN106728671 A CN 106728671A
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ethanol
pharmaceutical composition
percent concentration
extract
weight
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不公告发明人
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Jinan Haoyu Qingtian Medicine Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/894—Dioscoreaceae (Yam family)
    • A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/11—Aldehydes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/27—Asclepiadaceae (Milkweed family), e.g. hoya
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/55—Liquid-liquid separation; Phase separation

Abstract

Pharmaceutical composition of atraumatic restorative technique and preparation method thereof is treated the invention discloses a kind of, pharmaceutical composition of the present invention is with feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9 fluorine aldehyde C-9s as bulk drug, proportioning is formed, routinely various formulations can be made by preparation process, treatment atraumatic restorative technique is evident in efficacy.

Description

It is a kind of to treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof
Technical field
The invention belongs to technical field of traditional Chinese medicines, more particularly to a kind of pharmaceutical composition for treating atraumatic restorative technique And preparation method thereof.
Background technology
Atraumatic restorative technique is mainly because atraumatic factor causes femoral head inside poor arterial inflow, finally causes One process of femoral head inside bone necrosis living.Its incidence of disease is presented ascendant trend year by year to be increased.Its clinical symptoms is showed Occur based on pain and moving obstacle to suffer from hip.The cause of disease is more and the interpretation of the cause, onset and process of an illness is complicated, and severe patient can cause hip joint function tight Weight obstacle, has had a strong impact on patients ' life quality, and clinical trials difficult.The development of the medicine is to treatment atraumatic femoral head The curative effect of necrosis achieves obvious clinical effectiveness.
Feltwort:It is the herb of goatweed feltwort.Summer, autumn collection.Using fresh herb is dried in the shade.【Chemical composition】Herb Containing gossypose（raffinose）, stachyose（stach-yose）.Root cherry apple Ji coral glucoside, also containing stachyose, heptose （heptose）, octose（octose）, nonoses（nonose）Deng.Leaf contains rotenone（rotenone）It is thick with tonka-bean（coumarin）. Fruit ash content（ash）, produced containing aluminium, sodium, potassium, magnesium, fruit and separately contain stearic acid（Stearic acid), palmitic acid（palmitic acid）, oleic acid（oleic acid）, linoleic acid（linoleic acid）And cupreol（β-sitosterol）.【Pharmacology is made With】There is ganglionic blocking action the TA part of congener V.Nobille, therefore can reduce blood pressure.【Nature and flavor】Taste is pungent； It is bitter；It is cool in nature；Mild toxicity【Indication】It is clearing heat and detoxicating；Hemostasis stasis.Main pneumonia；Chronic appendicitis；Sore；Traumatic injury；Wound Bleeding.【Take passages】《Chinese book on Chinese herbal medicine》.
Cynanchum wilfordii：It is the root tuber of Asclepiadaceae plant cynanchum wilfordii.Autumn is harvested, and cleans, and section is dried【Proterties】Proterties differentiates Root cylinder or spindle, 10-20cm long, diameter 1-4cm, microbend, superficial white or yellow-white, have vertical wrinkle and skin of growing crosswise Hole, the aobvious yellow-white woody part of cork rent.Matter is hard, and plane of rupture is uneven, canescence, micro-strip powdery.Gas is micro-, and bitter is sweet.【Change Study point】Isolated cynanchum wilfordii glucoside in root（wilfoside）C3N、C1N、C2N、C3G、C1G、C2G、D1N、K1N、M1N、 F1N、W1N、G1G[.【Nature and flavor】It is sweet；Slight bitter；Slightly warm in nature；【Return through】Spleen；Stomach；Kidney channel.【Indication】Filling liver kidney；Strengthening the bones and muscles； Strengthening the spleen and stomach；Removing toxic substances.Main liver and kidney deficiency；Feel dizzy；Insomnia forgetfulness；Poliosis；Impotence；Seminal emission；Waist and knee acid is climbed；It is insufficiency of the spleen not Fortune；Abdominal fullness and distention；Ren is intended to depressed；Diarrhea；Postpartum breast is few；Lymphogranuloma inguinale sore.【Take passages】《Chinese book on Chinese herbal medicine》.
Duration and degree of heating root：It is the rhizome of Dioscoreaceae plant dioscorea zingiberensis wright.The rhizome honesty that vegetative propagation is cultivated 2 years can provide factory Production.Late November plant completely wither when can harvest, the silt on stem, fibrous root will be adopted and eliminated, thinly slice dry or Dry ventilation.But when silt is removed, be never soaked in water elutriation, because the Dioscin aglucon for being dissolved in water can be lost in.【Original shape State】Dioscorea zingiberensis wright, winds herbaceous species.Rhizome grows wild, nearly cylinder, finger-like or irregular branch, crust sepia when fresh, Section yellow, removes fibrous root and often leaves white spot printing after doing.Stem is left-handed, sometimes in branch or petiole base both sides micro-protuberance Or spinosity.Single leaf alternate；Petiole peltate raw；Blade ground paper matter, triangular shape is avette, heart-shaped or flechette-type, and usual 3 shallow split to 3 deep Split, middle sliver triangular shape is avette or lanceolar, two side slivers circle ear or Long Circle, surface green often have irregular patch, Cured leaf is in taupe.Male flower stockless, normal 2-3 fasciation rearranges into spike, the single branch of inflorescence, and 1 or 2-3 fascicled leaves Armpit,.Only 1-2 development is generally spent per cluster, base portion often has 3-4 pieces of film quality bract；Tapel 6, open and flat, aubergine when open is done Black afterwards；Stamen 6, is born in the edge of holder, and filigree is extremely short, several with flower pesticide isometric.Female inflorescence is several to male inflorescence similar；Female flower Tool staminodium.Capsule prismatic, per rib aliform.Black-and-blue after dry, surface is often by white powder；Seed is born in axis per room 2 Middle part, surrounding is with tunica albuginea shape wing.The month at florescence 5-8, the fruiting period 9-10 months.【Chemical composition】Containing diosgenin (Diosgenin). The content of diosgenin is reported as 1.05%, 3.3% and 3.4%-4.9% respectively.It is synthesis because the content of diosgenin is higher The very good material of adrenal cortex hormones drug.【Nature and flavor】Bitter；Micro-sweet；It is cool in nature；Mild toxicity.【Indication】Removing heat from the lung to relieve cough； Dampness removing is treating stranguria；Remove obstruction in channels to relieve pain；Removing toxicity for detumescence.Main cough with lung heat；It is damp and hot to drench pain；Lumbago due to wind-wetness evil；Carbuncle swells dislikes sore；Bruises and sprains；Honeybee Sting insect bite.【Take passages】《Chinese book on Chinese herbal medicine》.
Thick grass：It is the leaf of the narrow leaf fennel of Winteraceae plant.Spring, season in summer two pluck, and using fresh herb or dry use.【Original shape state】It is evergreen Shrub or dungarunga, 3-10m high.Bark, old branch taupe.Single leaf alternate or collection life；Petiole 7-15mm long；Leaf keratin, drapes over one's shoulders pin Shape, lanceolar or ellipse, 6-15cm long, 1.5-4.5cm wide, tip tail point or tapering, the narrow wedge shape of base portion, full edge.Edge Slightly warp, without hair, above green, it is glossy, below light green.Flower axillary or nearly basidixed, single raw or 2-3 collection leave armpit；Flower Obstruct 1.5-5cm long;Tapel 10-15, red to peony, maximum length of a film 7-12mm, 5-8mm wide；Stamen 6-11；Carpel 10-13,3.9-5.3mm long, style are upright, bore shape, 2-3.3mm long.Carpopodium 5.5cm long, dilute reachable 8cm；（Lv bones）（Lv dashes forward） Fruit 10-13, wooden, tip has tip that is long and bending.Seed is filbert, 7-7.5mm long, 5mm wide.The month at florescence 5-6, fruiting period 8- October.【Proterties】Proterties differentiates many shrinkages of the flat person of this product or broken.It is lanceolar, lanceolar or ellipse after complete person's flattening Shape, 6-15cm long, 1.5-4.5cm wide, the narrow wedge shape of base portion, the micro- warp in edge；Two sides green, below it is slightly weaker；Petiole 7-15mm long. Gas perfume (or spice) is strong, and taste is pungent is poisonous.【Pharmacological action】Branch, leaf, root, fruit poisonous, fruit, especially shell (Lv bones)（Lv dashes forward）Toxicity Greatly.Thick grass poisoning causes because its fruit is made into anistree eating by mistake more.Its toxic action is the mucous membrane that directly stimulates digestion, through digestion Road is absorbed into diencephalon, medulla oblongata, respiratory center and vasomotor center malfunction, well is benumbed motor nerve ending, seriously When damage brain.Poisoning symptom is similar to epilepsy, mainly faints from fear, and still spiritedness effect, clinical manifestation is have Nausea and vomiting, mouth Yearningly, diarrhoea, headache, dizziness, manic uneasiness, photis, arrhythmia cordis, numb limb, be short of breath, severe patient stupor, proverb, four Limb is twitched or paroxysmal convulsions, oliguria are to renal shutdown, dies from respiratory failure.Postmortem is shown in that nail is livid purple, facial and occipitalia subcutaneous hemorrhage, Brain, the heart, liver and the nephremia [4].The characteristics of thick grass slow poisoning is slow morbidity, without gastrointestinal symptom, is started with having a sleepless night, and is had Giddy, lassitude, general weakness, it is panic-stricken.Phonism photis, talk nonsense, paroxysmal faint from fear, whole body worm climb sense, four limbs Involuntary tic and obnubilation [5].The poisoning symptom of the animals such as dog, cat, mouse is similar to people, and postmortem finds：Dog lung There are hemorrhage and kidney, stomach, liver, cerebral blood stasis under hemorrhagic infarct, edema, serosa in portion, and mouse blood is dark red.Mouse peritoneal injection LD50：Fruit 0.7g/kg, pericarp o.5g/kg, seed 2.17g/kg, leaf 4.6g/kg, stem skin 5.1g/kg；It is hypodermic LD50:Fruit 0.66g/kg；The LD50 of intravenous injection:Fruit 0.425g/kg.Fruit flooding agent or seed pulvis are filled to cat and dog Stomach lethal dose（LD）0.4g/kg is, fruit is to mouse CD50（CD50）It is 0.813g/kg [2,6].People takes seed 5 ~8 can be poisoned.The toxicological effect of thick grass is similar to cocculin, is a kind of convulsivant, medulla oblongata of the site of action in brain stem Part, main poisoning symptom is spasm, and next has a series of autonomic nerves system symptoms such as Nausea and vomiting, gatism；But The incubation period and duration of shikimene poisoning are all more long than picrotoxin, there is good antagonism to barbital sodium.【Nature and flavor】 It is pungent；It is warm in nature；It is poisonous.【Indication】Wind-expelling pain-stopping；Dispersing swelling and dissipating binds；Desinsection is antipruritic.Main head wind；Skin is benumbed；Carbuncle swells；Acute mastitis； Scrofula；Larynx numbness；Hernia lump in the abdomen；Tinea scabies；The favus of the scalp；Wind carious pain；Body odour.【Take passages】《Chinese book on Chinese herbal medicine》.
Aluminum palmitate（Aluminum Palmitate）：Molecular formula：C48H93AlO6,Molecular weight：793.24, CAS accession number： 555-35-1.Boiling point：340.6°C at 760 mmHg（Calculated value）.Flash-point：154.1°C（Calculated value）.
9- fluorine aldehyde C-9s（9-Fluorononanal）：Molecular formula：C9H17FO,Molecular weight：160.23, CAS accession number：463- 25-2.Density：0.891g/cm3（Calculated value）.Boiling point：215.042°C at 760 mmHg（Calculated value）.Flash-point：102.759° C（Calculated value）.
2 chemical constitutions of bulk drug：
Aluminum palmitate（Aluminum Palmitate）9- fluorine aldehyde C-9s（9-Fluorononanal）.
The content of the invention
The purpose of the present invention is to overcome the shortcomings of background technology, there is provided a kind of effective treatment atraumatic restorative technique Pharmaceutical composition and preparation method thereof.
The present invention adopts the following technical scheme that realization：
The composition and weight portion for being made the bulk drug of the pharmaceutical composition of the treatment atraumatic restorative technique be：
2155-2255g of feltwort 8155-8255g cynanchum wilfordii 5655-5755g duration and degree of heating root 4255-4355g thick grass 78-88g of aluminum palmitate 125-135g 9- fluorine aldehyde C-9s.
The pharmaceutical composition for the treatment of atraumatic restorative technique is preferably used in, is by the bulk drug group of following weight portion Into：
Feltwort 8205g cynanchum wilfordii 5705g duration and degree of heating root 4305g thick grass 2205g aluminum palmitate 130g 9- fluorine aldehyde C-9s 83g。
A kind of pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that pharmaceutical composition can be using system The conventional method of agent prepares piece agent or capsule or dripping pill.
A kind of pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that pharmaceutical composition and chemical drugs or The treatment atraumatic restorative technique medicine of Chinese medicine composition.
A kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that as follows Prepare：
The composition and weight portion of bulk drug be：Feltwort 8155-8255g cynanchum wilfordii 5655-5755g duration and degree of heatings root 4255- 78-88g of 4355g thick grass 2155-2255g aluminum palmitate 125-135g 9- fluorine aldehyde C-9s；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
Preferred a kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that by such as It is prepared by lower step：
The composition and weight portion of bulk drug be：Feltwort 8205g cynanchum wilfordii 5705g duration and degree of heating root 4305g thick grass 2205g Aluminum palmitate 130g 9- fluorine aldehyde C-9s 83g；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
A kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that pharmaceutical composition Piece agent or capsule or dripping pill can be prepared using the conventional method of galenic pharmacy.
A kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that pharmaceutical composition With chemical drugs or Chinese medicine composition treatment atraumatic restorative technique medicine.
Specific embodiment
Embodiment 1：Treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：Feltwort 8205g Cynanchum wilfordii 5705g duration and degree of heating root 4305g thick grass 2205g aluminum palmitate 130g 9- fluorine aldehyde C-9s 83g；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
Embodiment 2：Treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：Feltwort 8155g Cynanchum wilfordii 5755g duration and degree of heating root 4255g thick grass 2255g aluminum palmitate 125g 9- fluorine aldehyde C-9s 88g；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
Embodiment 3：Treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：Feltwort 8255g Cynanchum wilfordii 5655g duration and degree of heating root 4355g thick grass 2155g aluminum palmitate 135g 9- fluorine aldehyde C-9s 78g；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
Embodiment 4：The preparation of tablet
The pharmaceutical composition 307g of Example 1, adds starch 103g, mixes, and granulation is dried, plus microcrystalline cellulose 35g, stearic Sour magnesium 3g, mixes, and is pressed into 1000, obtains final product medicinal composition tablets.
Embodiment 5：The preparation of capsule
The pharmaceutical composition 305g of Example 2, adds starch 87g, mixes, and granulation is dried, whole grain, adds appropriate magnesium stearate, Mix, encapsulated 1000, obtain final product medicament composition capsule.
Embodiment 6：The preparation of dripping pill
Weigh (80 DEG C) heating of Macrogol 6000 193g water-baths and boil molten, add the pharmaceutical composition 14g of embodiment 3, fully stir Mix uniform, with atoleine as cooling agent, put glass tube（4*80cm）In, chilling temperature is 5 DEG C, and drip internal-and external diameter is 7.0/ 2.0 (mm/mm), drip is 2.5cm away from liquid level, and drop speed is optimum condition with every point 61 drop, and the cold of dripping pill surface is blotted with cotton Solidifying agent, obtains final product medicament composition dropping pills.
Embodiment 7：Treat the pharmaceutical composition of atraumatic restorative technique
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：
Feltwort 5120g cynanchum wilfordii 5120g aluminum palmitate 42g 9- fluorine aldehyde C-9s 52g.
Embodiment 8：Treat the pharmaceutical composition of atraumatic restorative technique
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：
Feltwort 5070g cynanchum wilfordii 5170g aluminum palmitate 37g 9- fluorine aldehyde C-9s 57g.
Embodiment 9：Treat the pharmaceutical composition of atraumatic restorative technique
Treat atraumatic restorative technique pharmaceutical composition bulk drug composition and weight portion be：
Feltwort 5170g cynanchum wilfordii 5070g aluminum palmitate 47g 9- fluorine aldehyde C-9s 47g.
Experimental example 1：Treat the experimental study of atraumatic restorative technique
1 data and method
1.1 diagnostic criteria
According to《Disease of tcm Standardization of diagnosis and curative effect》In on caput femoris necrosis standard.1. symptom：Difficulty in walking, in limping, and And aggravated in progressive；Hip pain, predominantly adductor starting point, pain can be in intermittent or continuation；2. sign：Hip is closed Section can have surrounding tissue cramp；Hip joint function obstacle, predominantly inward turning abduction are limited, passive activity；3. after during x lines show Phase collapse of femoral head and femoral head density change x lines piece according to Ficat allotment methods：1. I phases：MRI is shown in that femoral head is believed extremely Number；Normal or slight change is shown in x-ray inspection, and joint space is normal；2. II phases：Femur head contour is normal, and x ray examinations show that sclerotin is dredged Pine, osteosclerosis etc., joint space is normal；3. III phases：Subchondral bone is collapsed, and femur head contour is interrupted, and joint space is without substantially narrow It is narrow；4. IV phases：Joint space narrows, and femoral head Xingtai substantially becomes inclined, and secondary hip osteoarthritis change.
1.2 clinical datas
Include the atraumatic restorative technique patient 124 that the court receives diagnosis and treatment during October 1 year December in 2014 Example.Control group (n=62) and observation group (n=62) are randomly divided into according to random digits table.In 62 patients of observation group, man 40 Example, female 22；27~57 years old age, average age (41.37 ± 10.37) year；Wherein steroid femur head necrosis 26, wine Essence caput femoris necrosis 27, alcohol and steroid femur head necrosis 4, the non-hormonal of non-alcoholic 5.Control group 62 In patient, man 40, female 22；26-58 years old ages, average age (42.14 ± 11.26) year；Wherein hormonal femoral head is bad Dead 27, Alcoholic Femoral Head Necrosis 27, alcohol and steroid femur head necrosis 3, the non-hormonal of non-alcoholic 5.Two Group patient's physical data Comparative result analysis shows difference does not have statistical significance (P>0.05), with comparativity.
1.3 inclusive criterias and exclusion standard
1.3.1 1. inclusive criteria meets diagnostic criteria person；2. age 2O -70 year old person；3. without obvious hip joint trauma history person；④ Meet the FieatII phases and the interim femorals head of III do not collapse denaturation person significantly；5. have excessive drinking history person or long-term use hormone history Person；6. signature Informed Consent Form and hospital correlation the Ethics Committee person of approving.
1.3.2 1. exclusion standard does not meet above-mentioned standard person；2. caused due to bone tuberculosis, bone tumour and osteomyelitis etc. ANFH person；3. the person that has severe mental disturbances；4. the dysfunction persons such as severe cardiac, liver, kidney are associated with；5. allergy body Matter person：6. gestation or women breast-feeding their children person.
1.4 treatment methods
1.4.1 control group uses western medical treatment.1. Western medicine：Alendronate sodium piece is given, per 5d1 times, 70mg/ times；2. operation side Method：Caudal anaesthesia, takes and lies on the back on traction table, by patient's suffering limb inward turning 15。, each abduction 30 of double lower limb。, using aseptic behaviour Make, 3 cm under hip greater trochanter that suffer from patient make a longitudinal incision, otch about 4~5cm, each layer tissue is cut dry, find greater trochanter Lower edge, then take diameter and be about 1 piece of Kirschner wire of 2.5 mm as guide pin, along patient's greater trochanter lower edge under C arm perspective Squeezed under femoral head at 0.5cm through neck of femur, to hardening zone, then using diameter be about the cavity ring of 8mm along guide pin hit the person to Under femoral head at 0.5cm, then hollow bone drill is taken out, its interior femoral head bone is left and does pathologic finding.Again by femoral head Capsula interna becomes tissue and is scraped with curet with hardening sequestrum, is suctioned out oozing of blood in pulp cavity using vacuum extractor, until new blood stream Go out.
1 .4.2 observation groups give the oral pharmaceutical composition on the basis of control group（The pharmaceutical composition lot number of embodiment 1 20141109）, each 2g, 2 times a day.Divide and take for 2 times sooner or later.Two groups of patients are with 1 month for 1 course for the treatment of.
1.5 efficacy assessment standards
Curative effect according to《New Chinese medicine guideline of clinical investigations》Middle related evaluation criteria.1. cure：Patient's hip joint without pain, Function is recovered substantially, and lower limb are without cripetura, and x ray examination results show that femoral head sequestrum area collapses, the phenomenon such as osteonecrosis disappears substantially Lose；2. effective x ray examinations show to be clearly better, and hip arthralgia disappears substantially；3. it is effective：X-ray inspection shows to have taken a turn for the better, and closes Section activity is extremely limited, and hip arthralgia is obviously improved；4. it is invalid：Compared with pre-treatment, hip joint changes with joint motion nothing It is kind, and x ray examinations are also unchanged.Total effective rate=cure rate+obvious effective rate+effective percentage.
Arthralgia standards of grading：1. 0 point：Standing walking or sitting and lying are painless；2. 2 points：Standing walking has Pain, but sitting and lying without pain；3. 4 points：Unbearably, sitting and lying occasionally has pain to standing walking pain；4. 6 points：Rest pain, pain More very.
1 .6 observation index
1. clinical cure rate, obvious effective rate, effective percentage and inefficiency after two groups of patient's treatments are observed；2. before observing two groups of patient's treatments Blood routine and changes of liver function afterwards；3. arthralgia scoring before and after two groups of patient's treatments is observed.
1.7 statistical methods
Carry out processing this group of data with statistical analysis treatment software SPSS22.0, wherein this Sets of Measurement Data and counting is provided Material is respectively adopted t inspections and x2Inspection, difference has statistical significance with P<0.05 represents.
2 results
2.1 two groups of Clinical efficacy comparisons
As seen from the results in Table 1, patient 14, effective patient 30, effective patient 13, refractory patient are cured after observation group's treatment 5；Cure patient 8, effective patient 23, effective patient 17, refractory patient 14 after control group treatment.Two groups of patients Not statistically significant (the P of comparing difference between total effective rate>0 .05).
1 two groups of patient clinical comparitive studies of table [example (%)]
2.2 two groups of patient's liver functions and blood routine change are compared
From the result of table 2, liver function and blood routine change comparing difference are not statistically significant before and after two groups of patient's treatments (P>0.05)。
Liver function and blood routine change are compared before and after 2 two groups of patient's treatments of table
2.3 two groups of patient articular's pain scores compare
The results are shown in Table 3.
Table 3 is treated front and rear two groups of patient articular's pain scores and is compared
From the result of table 3, treat preceding two groups of patient articular's pain scores comparing difference and do not have statistical significance (P> 0.05)；Two groups for the treatment of posterior joint pain scores have significant difference (P substantially compared with reduction before being treated between each group<0.05)； After observation group's treatment posterior joint pain scores are substantially less than control group treatment, and difference has statistical significance (P<0.05).

Claims (8)

1. a kind of pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that be made the raw material of the pharmaceutical composition The composition and weight portion of medicine be：
2155-2255g of feltwort 8155-8255g cynanchum wilfordii 5655-5755g duration and degree of heating root 4255-4355g thick grass 78-88g of aluminum palmitate 125-135g 9- fluorine aldehyde C-9s.
2. a kind of pharmaceutical composition for treating atraumatic restorative technique according to claim 1, it is characterised in that be made The composition and weight portion of the bulk drug of the pharmaceutical composition be：
Feltwort 8205g cynanchum wilfordii 5705g duration and degree of heating root 4305g thick grass 2205g aluminum palmitate 130g 9- fluorine aldehyde C-9s 83g。
3. a kind of pharmaceutical composition for treating atraumatic restorative technique according to claim 1, it is characterised in that medicine Composition can prepare piece agent or capsule or dripping pill using the conventional method of galenic pharmacy.
4. a kind of pharmaceutical composition for treating atraumatic restorative technique according to claim 1, it is characterised in that medicine The treatment atraumatic restorative technique medicine that composition is constituted with chemical drugs or Chinese medicine.
5. a kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique, it is characterised in that make as follows It is standby：
The composition and weight portion of bulk drug be：Feltwort 8155-8255g cynanchum wilfordii 5655-5755g duration and degree of heatings root 4255- 78-88g of 4355g thick grass 2155-2255g aluminum palmitate 125-135g 9- fluorine aldehyde C-9s；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
6. a kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique according to claim 5, it is special Levy is to prepare as follows：
The composition and weight portion of bulk drug be：Feltwort 8205g cynanchum wilfordii 5705g duration and degree of heating root 4305g thick grass 2205g Aluminum palmitate 130g 9- fluorine aldehyde C-9s 83g；
Preparation method：
（1）Feltwort, cynanchum wilfordii, duration and degree of heating root, thick grass, aluminum palmitate, 9- fluorine aldehyde C-9s are taken by bulk drug proportioning, is mixed, use weight The ethanol of percent concentration 11% takes as solvent in 21 DEG C of temperature extractions, and extraction time is 6 times, and each extraction time is 36 hours, Each solvent load is 46 times of bulk drug gross weight, is filtered, and obtains dregs of a decoction A and extract solution A, and extract solution A reclaims ethanol, is concentrated into Relative density 1.16, filtration, liquid is first washed with water, then use weight percent concentration by LSA-40 large pore resin absorption columns 46% ethanol solution elutes LSA-40 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 46%, reclaims ethanol, Concentrate drying, obtains final product extract A；
（2）Take step（1）Dregs of a decoction A, with the ethanol of weight percent concentration 51% as solvent, heating and refluxing extraction 6 times is carried every time The time is taken for 1.6 hours, each solvent load is 16 times of dregs of a decoction A weight, and filtration obtains dregs of a decoction B and extract solution B, and extract solution B is returned Ethanol is received, relative density 1.13 is concentrated into, filtered, liquid is first washed with water, then use weight by DM11 large pore resin absorption columns The ethanol solution of percent concentration 67% elutes DM11 large pore resin absorption columns, collects the ethanol eluate of weight percent concentration 67%, Ethanol is reclaimed, concentrate drying obtains final product extract B；
（3）Extract A and extract B are mixed, pharmaceutical composition is obtained final product.
7. a kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique according to claim 5, it is special Levy is that pharmaceutical composition can prepare piece agent or capsule or dripping pill using the conventional method of galenic pharmacy.
8. a kind of preparation method of the pharmaceutical composition for treating atraumatic restorative technique according to claim 5, it is special Levy is pharmaceutical composition and chemical drugs or Chinese medicine composition treatment atraumatic restorative technique medicine.
CN201611134497.1A 2016-12-10 2016-12-10 It is a kind of to treat pharmaceutical composition of atraumatic restorative technique and preparation method thereof Withdrawn CN106728671A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101700389A (en) * 2009-11-12 2010-05-05 刘艳菊 Traditional Chinese medicine composite for curing rheumatism and rheumatoid diseases
CN104435549A (en) * 2014-11-28 2015-03-25 方青春 Traditional Chinese medicine for treating wind-cold-dampness arthralgia type femoral head necrosis
CN105168306A (en) * 2015-09-09 2015-12-23 济南星懿医药技术有限公司 Pharmaceutical composition for promoting traumatic fracture coalescence

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101700389A (en) * 2009-11-12 2010-05-05 刘艳菊 Traditional Chinese medicine composite for curing rheumatism and rheumatoid diseases
CN104435549A (en) * 2014-11-28 2015-03-25 方青春 Traditional Chinese medicine for treating wind-cold-dampness arthralgia type femoral head necrosis
CN105168306A (en) * 2015-09-09 2015-12-23 济南星懿医药技术有限公司 Pharmaceutical composition for promoting traumatic fracture coalescence

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