CN102283947B - The application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine - Google Patents

The application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine Download PDF

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CN102283947B
CN102283947B CN201110211058.7A CN201110211058A CN102283947B CN 102283947 B CN102283947 B CN 102283947B CN 201110211058 A CN201110211058 A CN 201110211058A CN 102283947 B CN102283947 B CN 102283947B
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callicarpa nudiflora
rare
extract
dry
pharmaceutical composition
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CN102283947A (en
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谷陟欣
袁莉
颜冬兰
郗瑞云
卢捷
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Hainan Jiuzhitang Pharmacy Co., Ltd.
Jiuzhitang Co Ltd
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HAINAN JIUZHITANG PHARMACY CO Ltd
Jiuzhitang Co Ltd
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Abstract

The present invention relates to the application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine, this pharmaceutical composition take Callicarpa nudiflora extract as active component.Callicarpa nudiflora extract of the present invention has good effect to tissue adhesion, has the features such as inexpensive, safety is good.

Description

The application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine
Technical field
The present invention the present invention relates to a kind of application of pharmaceutical composition, particularly relates to it and is preparing the application in iatrotechnics posterior synechiae medicine.
Background technology
Tissue adhesion is still a still unsolved surgery difficult problem clinically so far.Adhesion is normal with after common abdominal cavity, gynecological, orthopedics and operation on vessels of heart.The generation of adhesion is prevented and treated clinically by improvement operation and auxiliary treatment.Auxiliary treatment mainly contains medicine and physical barriers two kinds of modes.The medicine of Western medicine control is mainly nonsteroidal antiinflammatory drug, corticosteroid, anticoagulant, enzyme, phosphatidylcholine and other classes.Blood circulation promoting regulates qi medicine is mainly used in Chinese herb prevention adhesion, as: Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Hirudo, the Radix Aucklandiae, Fructus Aurantii, Cortex Magnoliae Officinalis, Flos Carthami etc.; Stimulate purgatives medicine, the qi-activating drug of enterokinesia, as: Radix Et Rhizoma Rhei, Semen Persicae, the Radix Aucklandiae, Fructus Aurantii, Cortex Magnoliae Officinalis etc.; Qi-tonifying drug, as: the Radix Astragali, Radix Codonopsis etc.Biophysics barrier is mainly macromolecular solution barrier (as hyaluronic acid (HA) and derivant thereof) and mechanical barrier (as nonabsorable mechanical barriers such as Absorbable rod mechanical barrier and expanded polytetrafluoroethylsealing such as oxidized regenerated cellulose, biological absorbable Antiadhesive films).Research finds that physical barriers relates to again the evaluation to operation, operative doctor is difficult to accept, its curative effect also needs to be confirmed further, Western medicine untoward reaction comparatively large (as postponed wound healing etc.), and Chinese medicine has certain basis for tissue adhesion, as CN200910229786 mono-kind treats the Chinese medicine preparation of surgical intestinal adhesions, the Chinese medicine preparation of CN200610161271 prevention and therapy intestinal adhesion after abdominal cavity operation and method for making and application thereof.But what there is no that Callicarpa nudiflora is applied to tissue adhesion by any entity or individual at present makes correlational study.
Summary of the invention
The object of the present invention is to provide the application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine, this pharmaceutical composition take Callicarpa nudiflora extract as active component.
In the present invention, Callicarpa nudiflora extract is by one or more preparations in following method:
(1) adopt the fresh or dried feed of Callicarpa nudiflora, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract A;
(2) the fresh or dried feed of Callicarpa nudiflora is adopted, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use the ethanol elution of 10% ~ 90%, eluent filters, concentrated, dry Callicarpa nudiflora extract B;
(3) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, pressed liquor filters, and filtrate concentrates, dry Callicarpa nudiflora extract C, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract D;
(4) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution and pressed liquor merge, and filter, filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use the ethanol elution of 10% ~ 90%, eluent filters, concentrated, dry Callicarpa nudiflora extract E;
(5) adopt fresh or dry Callicarpa nudiflora raw material, to add water or rare alcohol or rare ketone solvent decoct secondary, collecting decoction, filter, concentrated, carry out membrane filtration, first use ultrafiltration, then nanofiltration, membrane material ceramic composite membrane and poly tetrafluoroethylene, concentrated, dry Callicarpa nudiflora F.
Pharmaceutical composition of the present invention can be for form of medication: oral agents, spray, injectable powder, injection.For increasing curative effect, two or more administering mode combined treatments wherein can be used.
Callicarpa nudiflora extract of the present invention has good effect to tissue adhesion, has the features such as inexpensive, safety is good.
Specific embodiment
embodiment 1
the preparation of Callicarpa nudiflora extract
By following any method preparation, get one or more mixing of a-f kind:
(1) adopt the fresh or dried feed of Callicarpa nudiflora, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract a;
(2) the fresh or dried feed of Callicarpa nudiflora is adopted, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use 10% ~ 90% ethanol elution, eluent filters, concentrated, dry Callicarpa nudiflora extract b;
(3) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, pressed liquor filters, and filtrate concentrates, dry Callicarpa nudiflora extract c, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract d;
(4) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution and pressed liquor merge, and filter, filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use the ethanol elution of 10% ~ 90%, eluent filters, concentrated, dry Callicarpa nudiflora extract e;
(5) adopt fresh or dry Callicarpa nudiflora raw material, to add water or rare alcohol or rare ketone decoct secondary, collecting decoction, filter, concentrated, carry out membrane filtration, first use ultrafiltration, then nanofiltration, membrane material ceramic composite membrane and poly tetrafluoroethylene, concentrated, dry Callicarpa nudiflora f.
embodiment 2
Get Callicarpa nudiflora leaf and twig 2.0kg(dry product), decoct with water secondary, 10 times amount, decoct 2 hours for the first time, second time 8 times amount, decoct 1 hour, collecting decoction, filter, be concentrated into 2000ml, carry out membrane filtration, first use ultrafiltration, then nanofiltration, membrane material ceramic composite membrane and poly tetrafluoroethylene, concentrated, dry, obtain 285.0g Callicarpa nudiflora extract, it is 14.25% that Callicarpa nudiflora extracts yield, and recording general flavone content is 113.7mg/g, and content of luteolin is that 1.27mg/g(is by dry product).
embodiment 3
Get Callicarpa nudiflora leaf and twig 2.0kg(fresh goods), add rare ketone and decoct secondary, each 10 times amount, decoct 2 hours, collecting decoction, filter, be concentrated into 2000ml, carry out membrane filtration, first use ultrafiltration, nanofiltration again, membrane material ceramic composite membrane and poly tetrafluoroethylene, concentrated, drying, obtains 129.2g Callicarpa nudiflora extract, and it is 6.46% that Callicarpa nudiflora extracts yield, recording general flavone content is 51.8mg/g, and content of luteolin is that 0.68mg/g(is by fresh goods).
embodiment 4
Get the fresh Callicarpa nudiflora leaf 1kg gathered October, add 2kg water and be broken into homogenate, squeezing, press residue adds the rare ketone heating extraction of 3kg, extracting solution and pressed liquor merge, filter, concentrated, dry 120.4g extract, it is 12.04% that Callicarpa nudiflora extracts yield, recording general flavone content is 56.9mg/g, and content of luteolin is 0.69mg/g, and total tannin content 14.22mg/g(is by fresh medical material).
embodiment 5
Get the fresh Callicarpa nudiflora leaf 1kg that JIUYUE is gathered, add 2kg water and be broken into homogenate, squeezing, press residue adds the rare alcohol heating extraction of 3kg, and extracting solution and pressed liquor merge, and filter, filtrate, by macroporous adsorbent resin column chromatography, washes cylinder with water, discards water lotion, use the ethanol elution of 70% again, de-liquid filters, concentrated, dry 95.2g extract, it is 9.52% that Callicarpa nudiflora extracts yield, and recording general flavone content is 59.8mg/g, and content of luteolin is that 0.78mg/g(is by fresh medical material).
embodiment 6
Get the fresh Callicarpa nudiflora leaf 1kg that JIUYUE is gathered, heating extraction twice, adds rare alcohol 8kg at every turn, extracts 2 hours, merging filtrate, filter, concentrated, dry 91.8g extract, it is 9.18% that Callicarpa nudiflora extracts yield, recording general flavone content is 48.7mg/g, and content of luteolin is 0.69mg/g, and total tannin content 13.55 mg/g(is by fresh medical material).
embodiment 7
Get Callicarpa nudiflora leaf and twig 2.0kg(dry product), heating extraction twice, add water 10kg at every turn, extracts 2 hours, merging filtrate, filter, concentrated, dry 491.3g extract, it is 24.56% that Callicarpa nudiflora extracts yield, recording general flavone content is 108.3mg/g, and content of luteolin is 1.35 mg/g, and total tannin content 41.7 mg/g(is by dry product).
embodiment 8
the Inhibition test of postoperative intestinal adhesion
If low high two dosage groups, be respectively 0.05g/kg and 0.5g/kg, by oral delivery form administration, separately establish positive drug group (sodium hyaluronate injection, Shandong Bausch & Lomb Freda Pharmaceutical Co., Ltd. produces) and normal blank matched group, often organize SD rat about 10 that is male, body weight 250-300g, totally 43 rats.
(1) experimental technique:
Rats underwent abdominal operation, the part serous coat (0.3 × 8cm) of wearing and tearing ileocecus ileum, causes rat abdominal cavity intestinal adhesion.Wherein positive drug group is after wearing and tearing serous coat, smears appropriate sodium hyaluronate injection in serous coat place with cotton swab, and postoperative stitching is steam again and raised.By rat random packet after whole operation terminates, often organize about 10.Successive administration is after 14 days, open abdominal cavity, adhesion degree is graded, evaluate intestinal adhesion with reference to Nair standard, 5 grades are divided according to the quantity of adhesive band, specific as follows: 0: completely without adhesion, 1: an adhesive band between internal organs or between internal organs and stomach wall, 2: two adhesive bands between internal organs or between internal organs and stomach wall, 3: more than two adhesive bands, and internal organs directly do not adhere to stomach wall, 4: internal organs directly adhere to stomach wall, and no matter adhesive band is how many.
Get portion of tissue simultaneously and do pathological observation assessment.Date processing adopts X 2 test.
(2) experimental result:
Postoperative each treated animal non-incision infects, and administration group compares with matched group, and control animals all sticks together, administration group Some Animals do not stick together or adhesion degree lighter.Compared with blank group, low dose group difference has significant, and high dose group and positive drug group difference tool are very significant.Show that medicine high dose group of the present invention improves rat tissue adhesion effectiveness comparison obvious.
Histological observation: between medication group, the difference of pathologic finding adhesion degree is not obvious, but is all obviously lighter than blank group, and serous coat is partly or entirely repaired, fibres visible cell, arrangement of collagen fibers is loosened irregular, and blood capillary proliferation is not obvious, sees a small amount of granulocyte and macrophage.Blank group adhesion organization fibroblast proliferation enlivens, collagen fiber dense arrangement, and blood capillary proliferation is obvious, granulocyte and macrophage more, peel off serous coat and have no reparation.
Table 2: extract of the present invention is to the inhibitory action (X ± SD) of rat postoperative intestinal adhesion
Compare with matched group: * P < 0.05; * p < 0.01
embodiment 9
prepared by tissue adhesion medicine
1, tablet preparation
By Callicarpa nudiflora extract 100g of the present invention, (in embodiment 1, extract a), starch 50g, microcrystalline Cellulose (lactose) 35g, carboxymethyl starch sodium 3g mix homogeneously, add 3% appropriate hypromellose alcoholic solution soft material, granulate with 18 mesh sieves, 60 ~ 70 DEG C of dryings, 18 mesh sieve granulate, add magnesium stearate 1.5g, mixing, is pressed into 1000, coating and get final product.
, capsule preparation
By Callicarpa nudiflora extract 100g of the present invention (in embodiment 5 extract), microcrystalline Cellulose 78g, adds 3% appropriate hypromellose alcoholic solution soft material, granulate with 18 mesh sieves, 60 ~ 70 DEG C of dryings, 18 mesh sieve granulate, magnesium stearate 1.5g mixes, and is filled to 1000.
, oral liquid preparation
By Callicarpa nudiflora extract 20g of the present invention (in embodiment 1 extract c), sucrose 200g, sodium benzoate 1.5g and distilled water 500ml dissolve, and are diluted with water to 1000ml, filter, fill (often propping up 10 milliliters), sterilizing and get final product.
, granule preparation
Get Callicarpa nudiflora extract 100g of the present invention (in embodiment 6 extract), sucrose 120g and 50% appropriate amount of ethanol, mixing, granulate, dry, granulate, subpackage and get final product.
, spray preparation
Get Callicarpa nudiflora extract 50g of the present invention (extract in embodiment 2), nipalgin 0.3g, adding distil water dissolves in right amount, and filter, then adding distil water is to 1000ml, fill, sterilizing and get final product.
, injection preparation
Get Callicarpa nudiflora extract 10g of the present invention (embodiment 3 is extract obtained), after adding 50ml water dissolution, add 100ml ethanol again, stir, cold preservation, precipitation, filters and reclaims ethanol, be concentrated into 25-30ml, then add ethanol and reach 80% to alcohol content, cold preservation filters, filtrate recycling ethanol, to without alcohol taste, adds benzyl alcohol 0.2g, sodium chloride 9g, stirring and dissolving, inject water to 1000ml, filter with G3 sintered glass funnel, fill, sterilizing and get final product.
, injectable powder preparation
Get Callicarpa nudiflora extract 100g of the present invention (embodiment 4 is extract obtained), after adding 150ml water dissolution, add 200ml ethanol again, stir, cold preservation, precipitation, filters and reclaims ethanol, be concentrated into 80-100ml, then add ethanol and reach 80% to alcohol content, cold preservation filters, filtrate recycling ethanol, to without alcohol taste, injects water to 150ml, filters with G3 sintered glass funnel, fill, sterilizing, be sub-packed in cillin bottle, lyophilization, tamponade, gland, obtains injectable powder.

Claims (3)

1. the application of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine, it is characterized in that this pharmaceutical composition with the Callicarpa nudiflora extract of effective dose for active component, this Callicarpa nudiflora extract is by one or more preparations in following method:
(1) adopt the fresh or dried feed of Callicarpa nudiflora, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract A;
(2) the fresh or dried feed of Callicarpa nudiflora is adopted, add water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use the ethanol elution of 10% ~ 90%, eluent filters, concentrated, dry Callicarpa nudiflora extract B;
(3) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, pressed liquor filters, and filtrate concentrates, dry Callicarpa nudiflora extract C, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution filters, and filtrate concentrates, dry Callicarpa nudiflora extract D;
(4) adopt the Callicarpa nudiflora raw material of fresh state, obtain pressed liquor and press residue through squeezing, press residue adds water or rare alcohol or rare ketone solvent, heating extraction, extracting solution and pressed liquor merge, and filter, filtrate passes through macroporous adsorbent resin column chromatography, wash cylinder with water, discard water lotion, then use the ethanol elution of 10% ~ 90%, eluent filters, concentrated, dry Callicarpa nudiflora extract E;
(5) adopt fresh or dry Callicarpa nudiflora raw material, to add water or rare alcohol or rare ketone decoct secondary, collecting decoction, filter, concentrated, carry out membrane filtration, first use ultrafiltration, then nanofiltration, membrane material ceramic composite membrane and poly tetrafluoroethylene, concentrated, dry Callicarpa nudiflora F.
2. application according to claim 1, is characterized in that described pharmaceutical composition can be for form of medication: oral agents, spray, injectable powder, injection.
3. pharmaceutical composition according to claim 2, is characterized in that, described take Callicarpa nudiflora extract as the dosage form dosage made of the pharmaceutical composition of active component for containing Callicarpa nudiflora total flavones 0.5-2 gram/day.
CN201110211058.7A 2011-07-27 2011-07-27 The application of a kind of pharmaceutical composition in preparation iatrotechnics posterior synechiae medicine Active CN102283947B (en)

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CN103816296B (en) 2012-11-19 2020-03-31 苏州润新生物科技有限公司 Callicarpa total glycoside extract and preparation method and application thereof
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CN113827649B (en) * 2021-11-11 2022-08-16 海南康盾生物制药有限公司 Medicament for postoperative rehabilitation of brain glioma and preparation method thereof

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