CN101433544B - External-use pharmaceutical composition formulation with antiphlogistic, swelling-dispersing and analgesic functions, and use - Google Patents
External-use pharmaceutical composition formulation with antiphlogistic, swelling-dispersing and analgesic functions, and use Download PDFInfo
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Abstract
The invention relates to an external pharmaceutical composition preparation with functions of resisting inflammation, reducing swelling and relieving pain, which is characterized in that the preparation is prepared by the following effective component raw materials in weight percent of the whole preparation: 0.01 to 20 percent of escin and/or pharmaceutically acceptable salt thereof, 0.01 to 10 percent of diclofenac or pharmaceutically acceptable salt thereof, and the balance being accessories. The external pharmaceutical composition can be made into any pharmaceutically acceptable external dosage form. The preparation can be used for treating symptoms, such as arthralgia, hyperosteogeny, gout, neuropathic pain, injuries from falls, chronic strain diseases and various closed injuries, and the like, and has strong practicability.
Description
Technical field
The present invention relates to a kind of is the external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity of raw material by natural drug and non-steroidal antalgic anti-inflammatory agent; The invention still further relates to the purposes of said preparation.
Background technology
Arthralgia, hyperosteogeny, gout, neuropathic pain, traumatic injury and various closed injurys etc. are commonly encountered diseases, frequently-occurring disease; Have a strong impact on people's work, study and daily life; Treat this type of disease oral, though the injection Chinese medicine and western medicine is a lot; But the mostly side effect of various degrees, to put the above-mentioned disease of external medication on the skin be easy, the most most popular method so stick, be coated with.
At present, the external preparation kind with anti-inflammatory and analgesic effect is more, and Western medicine is main with the non-steroidal antalgic anti-inflammatory agent, adopt dosage forms such as ointment, gel, but curative effect can not be lasting more, and the detumescence effect is not obvious, and has side effect such as allergy, zest.The then conventional dosage forms such as black plaster, rubber-emplastrum that adopt of Chinese medicine more.Black plaster is because of its determined curative effect, easy to use, low price; At folks of china use basis is widely arranged, but because of more mostly the preparation of plaster is to lean on experience, technological parameter and quality standard controlled in the production lack; Product quality is uneven; Be not suitable for large-scale industrialized production, and be prone to cause oil impregnate, leakage of oil, pollution clothes.Because the big compound recipe of the many employings of Chinese medicine, the rubber-emplastrum drug loading is limited, and curative effect is a greater impact.
The treatment of inflammation that aescine (or it is at pharmaceutically acceptable salt) can be used for causing like a variety of causes such as after wound, burn, scald, fracture, the operation and swelling and dysfunction of occurring together etc.Research shows that onset (just begins to show significantly antiinflammatory action) late after the seven leaf soap former times class administrations after 6 hours, and the appearance of antiinflammatory, anti-swelling effect has tangible time delay phenomenon, and acute inflammation and edema are produced certain adverse effect when treating.In addition, aescine (or it is at pharmaceutically acceptable salt) is mostly clinically to be the injection purposes, because the character of itself; Blood vessel had tangible zest; Cause very big misery to the patient, have in the therapeutic process shorten service time, therefore the effect of influence treatment.And oral diclofenac has GI irritation, can cause the distinct disadvantage of digestive tract hemorrhage, ulcer.
Summary of the invention
Technical problem to be solved by this invention is the deficiency to prior art, provide a kind of fill a prescription simple, preparation easily, determined curative effect, external-use pharmaceutical composition formulation that toxic and side effects is little with anti-inflammation detumescence analgesic activity.
Another technical problem to be solved by this invention has provided the purposes of external-use pharmaceutical composition formulation as previously discussed.
Technical problem to be solved by this invention is to realize through following technical scheme.The invention discloses a kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, be characterized in, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.01～20%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.01～10%;
All the other are adjuvant.
In the present invention, aescine and its are when pharmaceutically acceptable salt is selected for use simultaneously, and the two can adopt arbitrary proportion to mix.
Technical problem to be solved by this invention can also further realized by following technical scheme.Above-described preparation is characterized in, the percentage by weight that the active ingredient raw material accounts for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.1～5%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.01～5%.
Technical problem to be solved by this invention can also further realized by following technical scheme.Above-described preparation is characterized in, the percentage by weight that the active ingredient raw material accounts for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.1～5%.
Technical problem to be solved by this invention can also further realized by following technical scheme.Above-described preparation; Be characterized in; Described aescine is meant the total saponins that from Hippocastanaceae buckeye Heavenly Teacher chestnut, Aesculus chinensis Bunge, Radix Aesculi, Aesculus hippocastanum L. or Aesculus turbinata B1 seed, extracts, perhaps be meant state in the past extract in the seed with at least a in aescine A, aescine B, aescine C, aescine D, aescine E and the aescine F be the extract of main component; Described aescine is meant the salt that aforesaid aescine and pharmaceutically acceptable inorganic base or organic base reaction generate, preferred aescine sodium salt, aescine potassium salt, magnesium aescine, aescine calcium salt, arginine aescine, ornithine aescine, lysine aescine, histidine aescine, ethylenediamine aescine, diethylamine aescine, aescine monoethanolamine salt, diethanolamine aescine, triethanolamine aescine, aescine meglumine salt or aescine ammonium salt at pharmaceutically acceptable salt; Can choose wherein a kind of during use, also can choose in these 15 kinds the 2-15 kind with the mixture of arbitrary proportion mixing gained.
Aescine described in the present invention and its are at pharmaceutically acceptable salt; It can be commercially available aescine and it is at pharmaceutically acceptable salt; Also can be from Hippocastanaceae buckeye Heavenly Teacher chestnut, Aesculus chinensis Bunge, Radix Aesculi, Aesculus hippocastanum L. and Aesculus turbinata B1 seed, to extract the escin of gained or it is at pharmaceutically acceptable salt by conventional method for distilling; It also can be the aescine that disclosed any method for distilling extracted in the prior art and it is at pharmaceutically acceptable salt; Can also be with in aescine A, aescine B, aescine C, aescine D, aescine E and the aescine F at least a be extract or its of main component at pharmaceutically acceptable salt, preferred aescine or aescine; Described diclofenac or its are nonsteroidal antalgic and inflammation relieving chemical drugs at pharmaceutically acceptable salt, can be commercially available crude drug, also can be the synthetic crude drug of disclosed any method in the prior art.
Technical problem to be solved by this invention can also further realized by following technical scheme.Above-described preparation; Be characterized in; Described diclofenac is meant the salt that diclofenac and pharmaceutically acceptable inorganic base or organic base reaction generate, preferred diclofenac sodium, diclofenac potassium salt, diclofenac magnesium salt, diclofenac calcium salt, diclofenac arginine salt, diclofenac ornithine salt, diclofenac lysinate, diclofenac histidine salt, diclofenac ethylenediamine salt, diclofenac diethylammonium salt, diclofenac monoethanolamine salt, Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. salt, Diclofenac triethanolamine salt, diclofenac meglumine salt or diclofenac ammonium salt at pharmaceutically acceptable salt; Can choose wherein a kind of during use, also can choose in these 15 kinds the 2-15 kind with the mixture of arbitrary proportion mixing gained.
Preparation of the present invention can comprise tincture, ointment, ointment, gel, patch, membrane, cataplasma, lotion, liniment, aerosol, spray, rubber-emplastrum or liniment for any medically acceptable exterior-applied formulation.The required adjuvant of preparation can be disclosed any topical agent adjuvant applicatory in the prior art; Comprise required suitable substrate or excipient, the method for preparing of preparation can be taked disclosed any method applicatory in the prior art according to its dosage form.
Preparation of the present invention can be applicable to the treatment of arthralgia, hyperosteogeny, gout, neuropathic pain, traumatic injury, chronic strain disease and various closed injurys.
The inventor is according to following composition weight percent prescription, and all the other percetages by weight are required suitable substrate or excipient of preparation, make a kind of ointment:
Escin sodium 1%, diclofenac sodium 1% (being called for short QS ointment);
The inventor has carried out following pharmacodynamics screening.
With the above ointment that makes by following dosed administration:
QS small dose group: rat 1mg/kg, mice 2mg/kg;
Dose groups among the QS: rat 6mg/kg, mice 12mg/kg;
The heavy dose of group of QS: rat 36mg/kg, mice 72mg/kg.
Medicine efficacy screening 1:QS ointment is to the influence of rat experiment property arthritis model.
1.1 experimental technique:
Test method: get rat and be divided into 5 groups at random, 10 every group.The model preparation is employed in every right back sufficient pad intradermal injection adjuvant 0.1ml of portion of rat, brings out arthritic generation.With incomplete Freund (IFA) and bacillus calmette-guerin vaccine (BCG) emulsifying mixing, the BCG final concentration is 10mg/ml.
The 30min preventive administration is 1 time before influence to primary affection: the Yu Zhiyan, observes causing scorching back 18h adjuvant injection side vola swelling degree, representes with miking vola thickness, takes the mean and matched group compares, and carries out statistical test.
Influence to polyarthritis: beginning on the 8th administration in adjuvant injection back, every day 1 time, successive administration to the 30 days is observed the preventive and therapeutic effect of polyarthritis.From the self administration of medication, every at a distance from 1 week, with the former degree of the left back vola of miking rat (adjuvant injection offside is represented with mm),, take the mean and the matched group comparison as the swelling degree index of multiple pathological changes, carry out statistical test.
Influence to the general pathological changes: remove the swelling degree of observing left back foot (adjuvant injection offside); Outside the index as polyarthritis, also observe forelimb, ear and general pathological changes such as the afterbody pathological changes incidence rate and the order of severity, by 0 grade～4 grades point system records; 0=is normal; 1=is only red, 2=is red add light swollen, the seriously swollen .4=joint deformity, tetanic of 3=.Take the mean and carry out statistical test.
1.2 experimental result
Results suggest, QS ointment can alleviate the generation of rat assist agent arthritis constitutional pathological changes, multiple pathological changes, can stop the generation of general pathological changes equally.Relatively there were significant differences (p＜0.05, p＜0.01) with blank control group.Prompting QS ointment has the arthritic effect of significant anti-experimental character.See table 1,2,3.
Table 1 QS ointment is to the influence
of experimental arthritis constitutional pathological changes
| Group | Dose (mg/kg) | Number of animals (only) | Constitutional pathological changes swelling degree (mm) |
| The heavy dose of group of dose groups QS ointment in the blank control group diclofenac emulsion group QS ointment small dose group QS ointment | - 6 1 6 36 | 10 10 10 10 10 | 5.351±0.706 4.605±0.544 ** 3.927±0.427 ** 3.526±0.543 ** 3.138±0.556 ** |
Annotate: compare with blank control group,
*P＜0.01.
Table 2 QS ointment is to the influence
of the multiple pathological changes of experimental arthritis
| Group | Dose (mg kg) | Number of animals (only) | Swelling degree (mm) | ? | ? |
| The 15th day | The 22nd day | The 30th day | ? | ? | ? |
| The heavy dose of group of dose groups QS ointment in the blank control group diclofenac emulsion group QS ointment small dose group QS ointment | - 6 1 6 36 | 10 10 10 10 10 | 5.712 ±0.553 5.237 ±0.444 * 4.557 ±0.448 ** 4.332 ±0.552 ** 4.140 ±0.627 ** | 6.246 ±0.449 5.774 ±0.465 * 4.998 ±0.457 ** 4.597 ±0.347 ** 4.349 ±0.338 ** | 6.432 ±0.607 5.907 ±0.447 * 5.227 ±0.318 ** 5.140 ±0.379 ** 5.006 ±0.217 ** |
Annotate: compare with blank control group,
*P＜0.05,
*P＜0.01.
Table 3 QS ointment is to the influence
of experimental arthritis whole body pathological changes
| Group | Dose (mg/kg) | Number of animals (only) | The scoring of whole body pathological changes |
| Blank control group diclofenac emulsion group | - 6 | 10 10 | 3.20±0.46 2.99±0.67 |
| The heavy dose of group of dose groups QS ointment in the QS ointment small dose group QS ointment | 1 6 36 | 10 10 10 | 2.66±0.52 * 2.45±0.76 * 2.33±1.07 * |
Annotate: compare with blank control group,
*P＜0.05,
*P＜0.01.
Medicine efficacy screening 2:QS ointment is to the influence of Oleum Tiglii induced mice ear swelling.
2.1 experimental technique:
Get normal ICR mice, body weight 25～28g, male.Be divided into 5 groups at random, every group of 10 mices.The even coating in mouse ear two sides, coating is 3 continuously, twice of every day.Behind the last coating 1h on the 3rd, each administration group is cleaned with dry cotton ball with distilled water flush away plaster.Be applied to two sides before and after the ear of a mice left side with 2% Oleum Tiglii (containing 2% Oleum Tiglii, 5% water, 20% ethanol and 73% ether) 0.05ml; After causing scorching 4h, put to death mice; Two ears about cutting along the auricle baseline, (diameter 9mm) takes off round auricle, scales/electronic balance weighing at same position respectively with card punch; As auricular concha swelling degree, and calculate the swelling percentage rate with the difference of mice left and right sides auricular concha weight.
2.2 experimental result:
QS ointment all can alleviate Oleum Tiglii and cause the mice ear rate, has compared significant difference (p＜0.05, p＜0.01) with blank control group.Point out medicine to have and obviously alleviate the effect that Oleum Tiglii causes mice swelling and inflammation.The result sees table 4.
Table 4 QS ointment is to the influence
of Oleum Tiglii induced mice ear swelling
| Group | Dose (mg/kg) | Number of animals (only) | Swelling rate (%) |
| The heavy dose of group of dose groups QS ointment in the blank control group diclofenac emulsion group QS ointment small dose group QS ointment | - 12 2 12 72 | 10 10 10 10 10 | ?187.46±50.13?140.46±46.78 * ?123.47±57.78 * ?119.33±40.18 ** ?106.07±66.35 ** |
Annotate: compare with blank control group,
*P＜0.05,
*P＜0.01.
Medicine efficacy screening 3:QS ointment stimulates the influence that causes the mice pain reaction to the acetic acid abdominal cavity.
3.1 experimental technique:
Get the ICR mice; About body weight 17～21g, ♀
half and half.Be divided into 5 groups at random, 20 every group.The even coating of mouse peritoneal face, behind the coating 30min, each administration group is cleaned with dry cotton ball with distilled water flush away plaster.Each is organized mouse peritoneal and only injects 0.5% acetic acid 0.2ml/, respectively organizes writhing response number of animals and the writhing response number of times that mice occurs in the 15min behind the observation injection acetic acid.The result carries out x2 check (enumeration data) and t check (measurement data).
3.2 experimental result
Experimental result shows that QS ointment group does not have the writhing response number of animals apparently higher than the blank group, with the blank group significant difference (p＜0.05, P＜0.01) is arranged more all; QS ointment group can reduce the mouse writhing reaction times, with the blank group significant difference (p＜0.01) is arranged more all.The mice pain reaction that shows QS ointment group that acetic acid is stimulated and cause has the obvious suppression effect.The result sees table 5.
Table 5 QS ointment stimulates the influence
that causes the mice pain reaction to acetic acid
| Group | Dose (mg/kg) | Number of animals (only) | No writhing response number of animals (only) | Writhing response number of times in the 15min |
| The heavy dose of group of dose groups QS ointment in the blank group diclofenac emulsion group QS ointment small dose group QS ointment | - 12 ?2 12 72 | 20 20 ?20 20 20 | 0 10 ** ?9 ** 10 ** 12 ** | 44.3±7.9 30.8±11.1 ** ?32.5±13.2 ** 28.9±12.5 ** 24.3±14.6 ** ? |
Compare with the blank group,
*P＜0.05,
*P＜0.01.
The medicine efficacy screening brief summary: results suggest, QS ointment can alleviate the generation of rat assist agent arthritis constitutional pathological changes, multiple pathological changes, can stop the generation of general pathological changes equally.Explain that QS ointment has the arthritic effect of significant anti-experimental character.QS ointment can also alleviate Oleum Tiglii and cause the mice ear rate, has obviously to alleviate the effect that Oleum Tiglii causes mice swelling and inflammation.QS ointment can also obviously reduce acetic acid and stimulate the mouse writhing reaction times, explains that the mice pain reaction that medicine causes the acetic acid stimulation has the obvious suppression effect.
In above-mentioned experiment, three dose groups that designed all have tangible antiinflammatory, detumescence and analgesic effect.Three dosage according to the dose,equivalent conversion to the adult be about 10,60, about the 360mg/60kg body weight.Pointing out pharmaceutical composition adult of the present invention dosage scope on the one is 10～360mg/60kg body weight.
Preparation of the present invention is a kind of external preparation, uses it can reduce untoward reaction and zest that medicine is caused by vivo medicine-feeding greatly.Non-steroidal antalgic anti-inflammatory agent diclofenac or its have analgesia, antiinflammation is strong, onset is rapid, dosage is low, individual variation is little characteristics at pharmaceutically acceptable salt; Show through research; Aescine (or it is at pharmaceutically acceptable salt) share with diclofenac can obviously play synergism, thus the characteristics that the performance onset is rapid, effect is strong, duration of effect is long.
Compared with prior art; Pharmaceutical composition of the present invention and preparation thereof have the following advantages: 1, good effect: the effective percentage that topical composition preparation of the present invention is treated various closed soft tissue injuries through clinical trial reaches 92.1%; The compatibility and the addition of its basis, auxiliary composition draw through repetition test; Put on the skin in the affected part and to be coated with every day 2-3 time; Onset time is fast, effect is strong, effect is held time length.2, prescription element is few, makes simply, and is easy to use, thereby easy to implement; 3, be widely used; All kinds of inflammation, acute and chronic pain disease all there is the obvious treatment mitigation; Can be used for treating diseases such as arthralgia, hyperosteogeny, gout, neuropathic pain, traumatic injury, chronic strain disease and various closed injurys, thus practical.
The specific embodiment
Below the nonrestrictive part embodiment that the present invention relates to that enumerated.
Embodiment 1.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine or it is at pharmaceutically acceptable salt 0.01%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.01%;
All the other are adjuvant.
Embodiment 2.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 20%;
(2) diclofenac or it is at pharmaceutically acceptable salt 10%;
All the other are adjuvant.
Embodiment 3.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine or it is at pharmaceutically acceptable salt 0.01%;
(2) diclofenac or it is at pharmaceutically acceptable salt 10%;
All the other are adjuvant.
Embodiment 4.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine or it is at pharmaceutically acceptable salt 20%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.01%;
All the other are adjuvant.
Embodiment 5.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine or it is at pharmaceutically acceptable salt 0.05%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.1%;
All the other are adjuvant.
Embodiment 6.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 6%;
(2) diclofenac or it is at pharmaceutically acceptable salt 6%;
All the other are adjuvant.
Embodiment 7.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 10%;
(2) diclofenac or it is at pharmaceutically acceptable salt 8%;
All the other are adjuvant.
Embodiment 8.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 15%;
(2) diclofenac or it is at pharmaceutically acceptable salt 9%;
All the other are adjuvant.
Embodiment 9.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 18%;
(2) diclofenac or it is at pharmaceutically acceptable salt 7%;
All the other are adjuvant.
Embodiment 10.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 12%;
(2) diclofenac or it is at pharmaceutically acceptable salt 5.5%;
All the other are adjuvant.
Embodiment 11.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.05%.
All the other are adjuvant.
Embodiment 12.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 5%;
(2) diclofenac or it is at pharmaceutically acceptable salt 5%.
All the other are adjuvant.
Embodiment 13.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 1%.
All the other are adjuvant.
Embodiment 14.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.5%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.05%.
All the other are adjuvant.
Embodiment 15.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.2%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.1%.
All the other are adjuvant.
Embodiment 16.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.8%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.5%.
All the other are adjuvant.
Embodiment 17.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1.5%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.8%.
All the other are adjuvant.
Embodiment 18.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 2%;
(2) diclofenac or it is at pharmaceutically acceptable salt 1.5%.
All the other are adjuvant.
Embodiment 19.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 3%;
(2) diclofenac or it is at pharmaceutically acceptable salt 2%.
All the other are adjuvant.
Embodiment 20.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 4%;
(2) diclofenac or it is at pharmaceutically acceptable salt 3%.
All the other are adjuvant.
Embodiment 21.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 4.2%;
(2) diclofenac or it is at pharmaceutically acceptable salt 4.5%.
All the other are adjuvant.
Embodiment 22.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 0.1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 5%.
All the other are adjuvant.
Embodiment 23.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 5%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.01%.
All the other are adjuvant.
Embodiment 24.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.1%.
All the other are adjuvant.
Embodiment 25.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 5%.
All the other are adjuvant.
Embodiment 26.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.5%.
All the other are adjuvant.
Embodiment 27.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 2%.
All the other are adjuvant.
Embodiment 28.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 3%.
All the other are adjuvant.
Embodiment 29.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 4%.
All the other are adjuvant.
Embodiment 30.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 2.5%.
All the other are adjuvant.
Embodiment 31.In any one described preparation of embodiment 1-30; Described aescine is meant the total saponins that from Hippocastanaceae buckeye Heavenly Teacher chestnut, Aesculus chinensis Bunge, Radix Aesculi, Aesculus hippocastanum L. or Aesculus turbinata B1 seed, extracts, perhaps be meant state in the past extract in the seed with at least a in aescine A, aescine B, aescine C, aescine D, aescine E and the aescine F be the extract of main component; Described aescine is meant the salt that aforesaid aescine and pharmaceutically acceptable inorganic base or organic base reaction generate at pharmaceutically acceptable salt.
Embodiment 32.In any one described preparation of embodiment 1-31, a kind of among pharmaceutically acceptable salt is meant 15 kinds of aescine sodium salt, aescine potassium salt, magnesium aescine, aescine calcium salt, arginine aescine, ornithine aescine, lysine aescine, histidine aescine, ethylenediamine aescine, diethylamine aescine, aescine monoethanolamine salt, diethanolamine aescine, triethanolamine aescine, aescine meglumine salt or aescine ammonium salts of described aescine.
Embodiment 33.In any one described preparation of embodiment 1-31, the 2-14 kind of described aescine among pharmaceutically acceptable salt is meant 15 kinds of aescine sodium salt, aescine potassium salt, magnesium aescine, aescine calcium salt, arginine aescine, ornithine aescine, lysine aescine, histidine aescine, ethylenediamine aescine, diethylamine aescine, aescine monoethanolamine salt, diethanolamine aescine, triethanolamine aescine, aescine meglumine salt or aescine ammonium salts is with the mixture of arbitrary proportion mixing gained.
Embodiment 34.In any one described preparation of embodiment 1-31, described aescine is meant aescine sodium salt, aescine potassium salt, magnesium aescine, aescine calcium salt, arginine aescine, ornithine aescine, lysine aescine, histidine aescine, ethylenediamine aescine, diethylamine aescine, aescine monoethanolamine salt, diethanolamine aescine, triethanolamine aescine, aescine meglumine salt and 15 kinds of mixture of aescine ammonium salt at pharmaceutically acceptable salt.
Embodiment 35.In any one described preparation of embodiment 1-34, described diclofenac is meant the salt that diclofenac and pharmaceutically acceptable inorganic base or organic base reaction generate at pharmaceutically acceptable salt.
Embodiment 36.In any one described preparation of embodiment 1-35, a kind of among pharmaceutically acceptable salt is meant 15 kinds of diclofenac sodium, diclofenac potassium salt, diclofenac magnesium salt, diclofenac calcium salt, diclofenac arginine salt, diclofenac ornithine salt, diclofenac lysinate, diclofenac histidine salt, diclofenac ethylenediamine salt, diclofenac diethylammonium salt, diclofenac monoethanolamine salt, Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. salt, Diclofenac triethanolamine salt, diclofenac meglumine salt or diclofenac ammonium salts of described diclofenac.
Embodiment 37.In any one described preparation of embodiment 1-35, described diclofenac among pharmaceutically acceptable salt is meant 15 kinds of diclofenac sodium, diclofenac potassium salt, diclofenac magnesium salt, diclofenac calcium salt, diclofenac arginine salt, diclofenac ornithine salt, diclofenac lysinate, diclofenac histidine salt, diclofenac ethylenediamine salt, diclofenac diethylammonium salt, diclofenac monoethanolamine salt, Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. salt, Diclofenac triethanolamine salt, diclofenac meglumine salt or diclofenac ammonium salts the 2-14 kind with the mixture of arbitrary proportion mixing gained.
Embodiment 38.In any one described preparation of embodiment 1-35, described diclofenac is meant the mixture of 15 kinds of diclofenac sodium, diclofenac potassium salt, diclofenac magnesium salt, diclofenac calcium salt, diclofenac arginine salt, diclofenac ornithine salt, diclofenac lysinate, diclofenac histidine salt, diclofenac ethylenediamine salt, diclofenac diethylammonium salt, diclofenac monoethanolamine salt, Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. salt, Diclofenac triethanolamine salt, diclofenac meglumine salt and diclofenac ammonium salts at pharmaceutically acceptable salt.
Embodiment 39.In any one described preparation of embodiment 1-38; Its dosage form is any medically acceptable exterior-applied formulation, comprises tincture, ointment, ointment, gel, patch, membrane, cataplasma, lotion, liniment, aerosol, spray, rubber-emplastrum or liniment.Used adjuvant can be selected conventional adjuvant for use by dosage form, adds the external used medicine that the active ingredient raw material is processed corresponding dosage form by conventional method again.
Embodiment 40.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts aescine 1% (percentage by weight, down together), diclofenac 1%, and medium carrier adopts vaseline, liquid Paraffin, ethyl hydroxybenzoate, makes ointment.Be used for local muscle treatment of pain.Embodiment 41.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts aescine 1.5% (percentage by weight, down together), diclofenac sodium 0.3%, and medium carrier adopts vaseline, liquid Paraffin, ethyl hydroxybenzoate, makes ointment.Being used for treatment sprains.
Embodiment 42.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts aescine A 0.01% (percentage by weight, down together), diclofenac 1.5%, and medium carrier adopts carbopol, and ethanol, glycerol, Polysorbate, ethyl hydroxybenzoate, sodium hydroxide, distilled water make gel.Be used to treat cervical vertebra pain.
Embodiment 43.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts aescine B 0.9% (percentage by weight, down together), diclofenac 1.2%, adopts 60% ethanol dilution, makes tincture.Be used to treat arthralgia.
Embodiment 44.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts arginine aescine 1.5% (percentage by weight; Diclofenac 0.6% down together); Medium carrier adopts sodium polyacrylate; Starch propionate, methyl hydroxybenzoate, third of nipalgin, Polysorbate, vinyl acetate, dried aluminum hydroxide gel, water make cataplasma.Be used to treat hyperosteogeny.
Embodiment 45.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts magnesium aescine 1.1% (percentage by weight, down together), diclofenac potassium 0.4%, and medium carrier adopts dibutyl phthalate, polyvinyl formal-acetal, acetone, 70% ethanol, makes liniment.Be used to treat traumatic injury.
Embodiment 46.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts lysine aescine 1.8% (percentage by weight, down together), diclofenac ethylenediamine 0.3%, and medium carrier adopts Polysorbate, glycerol, potassium sorbate, ethylparaben, makes lotion.Be used to treat chronic muscular strain.
Embodiment 47.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts histidine aescine 1% (percentage by weight, down together), diclofenac meglumine 0.5%, and medium carrier adopts propylene glycol, ethanol, laurocapram, ethylparaben, makes liniment.Be used to treat lumbar vertebra pain.
Embodiment 48.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts ethylenediamine aescine 0.01% (percentage by weight, down together), Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. 1%, and medium carrier adopts rubber, Colophonium, vaseline, white oil, lanoline, dimethyl sulfoxine, laurocapram, makes rubber-emplastrum.Be used for treatment of arthritis.
Embodiment 49.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts diethylamine aescine 0.01% (percentage by weight, down together), diclofenac magnesium 1%, and medium carrier adopts medical PVA, and distilled water, propylene glycol make membrane.Be used to treat muscle sprain.
Embodiment 50.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts diethanolamine aescine 0.01% (percentage by weight, down together), diclofenac 1%, and medium carrier adopts polyvinyl alcohol, polyvidone, propylene glycol, laurocapram, makes patch.Be used to treat the partial gall that fracture causes.
Embodiment 51.A kind of external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity.Present embodiment adopts triethanolamine aescine 0.8% (percentage by weight, down together), diclofenac 0.3%, and medium carrier adopts 95% ethanol, dichlorodifluoromethane, makes aerosol.Be used to treat cancer pain.
Claims (6)
1. the external-use pharmaceutical composition formulation with anti-inflammation detumescence analgesic activity is characterized in that, the percentage by weight of processing the active ingredient raw material of medicine and accounting for total formulation is:
(1) aescine and it is at pharmaceutically acceptable salt 1%;
(2) diclofenac or it is at pharmaceutically acceptable salt 0.1～5%;
All the other are adjuvant;
Its dosage form is any medically acceptable exterior-applied formulation, comprises tincture, ointment, ointment, gel, patch, membrane, cataplasma, lotion, liniment, aerosol, spray, rubber-emplastrum or liniment.
2. preparation according to claim 1; It is characterized in that; Described aescine is meant the total saponins that from Hippocastanaceae buckeye Heavenly Teacher chestnut, Aesculus chinensis Bunge, Radix Aesculi, Aesculus hippocastanum L. or Aesculus turbinata B1 seed, extracts, perhaps be meant state in the past extract in the seed with at least a in aescine A, aescine B, aescine C, the aescine D be the extract of main component; Described aescine is meant the salt that aforesaid aescine and pharmaceutically acceptable inorganic base or organic base reaction generate at pharmaceutically acceptable salt.
3. preparation according to claim 1; It is characterized in that described aescine is meant in aescine sodium salt, aescine potassium salt, magnesium aescine, aescine calcium salt, arginine aescine, ornithine aescine, lysine aescine, histidine aescine, ethylenediamine aescine, diethylamine aescine, aescine monoethanolamine salt, diethanolamine aescine, triethanolamine aescine, aescine meglumine salt or the aescine ammonium salt one or more mixture at pharmaceutically acceptable salt.
4. preparation according to claim 1 is characterized in that, described diclofenac is meant the salt that diclofenac and pharmaceutically acceptable inorganic base or organic base reaction generate at pharmaceutically acceptable salt.
5. preparation according to claim 1; It is characterized in that described diclofenac is meant in diclofenac sodium, diclofenac potassium salt, diclofenac magnesium salt, diclofenac calcium salt, diclofenac arginine salt, diclofenac ornithine salt, diclofenac lysinate, diclofenac histidine salt, diclofenac ethylenediamine salt, diclofenac diethylammonium salt, diclofenac monoethanolamine salt, Bis(2-hydroxyethyl)ammonium 2-(2,6-dichlorophenylamino)phenylacetate. salt, Diclofenac triethanolamine salt, diclofenac meglumine salt or the diclofenac ammonium salt one or more mixture at pharmaceutically acceptable salt.
6. the application of preparation as claimed in claim 1 in the medicine of preparation treatment arthralgia, hyperosteogeny, gout, neuropathic pain, traumatic injury, chronic strain disease and various closed injurys.
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| CN102048745A (en) * | 2009-10-30 | 2011-05-11 | 重庆医药工业研究院有限责任公司 | Compound sodium aescinate cataplasm |
| CN104622740B (en) * | 2015-01-14 | 2017-05-31 | 武汉爱民制药股份有限公司 | Purposes of the Horse chest Nut P.E in cosmeceutical is prepared |
| CN105878173B (en) * | 2016-04-13 | 2018-10-19 | 武汉爱民制药股份有限公司 | A kind of Sodium Aescinate liniment |
| CN106943381B (en) * | 2017-04-01 | 2021-12-14 | 武汉爱民制药股份有限公司 | Aescin A enteric slow-release pellet and preparation method thereof |
| CN112972385B (en) * | 2021-02-26 | 2022-03-29 | 广东同德药业有限公司 | Inflammation-diminishing and pain-relieving aerosol and preparation method thereof |
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| CN1130350A (en) * | 1994-07-07 | 1996-09-04 | 株式会社资生堂 | Dermatologic preparation |
| CN1151285A (en) * | 1995-12-05 | 1997-06-11 | 中山医科大学科技开发部 | Diclofenac ointment and its prepn. method |
| CN1491657A (en) * | 2002-10-25 | 2004-04-28 | 山东绿叶制药股份有限公司 | Medicinal composition for injection, preparation containing said medicinal composition and its preparing process |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1130350A (en) * | 1994-07-07 | 1996-09-04 | 株式会社资生堂 | Dermatologic preparation |
| CN1151285A (en) * | 1995-12-05 | 1997-06-11 | 中山医科大学科技开发部 | Diclofenac ointment and its prepn. method |
| CN1491657A (en) * | 2002-10-25 | 2004-04-28 | 山东绿叶制药股份有限公司 | Medicinal composition for injection, preparation containing said medicinal composition and its preparing process |
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