CN102451463B - Naja naja atra analgesic peptide transdermal preparation - Google Patents
Naja naja atra analgesic peptide transdermal preparation Download PDFInfo
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- CN102451463B CN102451463B CN201010516449.5A CN201010516449A CN102451463B CN 102451463 B CN102451463 B CN 102451463B CN 201010516449 A CN201010516449 A CN 201010516449A CN 102451463 B CN102451463 B CN 102451463B
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Abstract
The invention discloses a naja naja atra analgesic peptide transdermal preparation. The transdermal preparation consists of naja naja atra analgesic peptide lyophilized powder and an adhesive which comprises 1 to 15 percent of transdermal enhancer. The naja naja atra analgesic peptide transdermal preparation can be absorbed well through skin, can be directly coated on a painful part, can be released a sustained and controlled way, has a good analgesic effect, and is safe and reliable, and convenient to use. The naja naja atra analgesic peptide transdermal preparation is easy to prepare; only the adhesive is prepared in advance, the naja naja atra analgesic peptide lyophilized powder is added into the adhesive and mixed uniformly, mixture is coated and dried, and then a lining is coated; and quality is easy to control, and production cost of the preparation is greatly reduced compared with that of injection.
Description
Technical field
The present invention relates to a kind of analgesia preparation, particularly a peptide species class preparation capable of permeating skin.
Background technology
Analgesics can the intractable pain such as misery, particularly arthralgia, trigeminal neuralgia, nervous headache, sciatica, lepra reaction neuralgia, cancer pain at late stage of reduction of patient.
Existing analgesics, is generally oral formulations, and analgesic effect is poor, and action time is short, can not the slight illness of effective reduction of patient.The medicine that existing analgesic effect is good has the polypeptide extracted from snake venom.
As far back as 20 beginnings of the century, people just start to apply snake venom to alleviate malignant, tumor pain, neuropathic pain, intractable pain and arthralgia.1933, Chen and Robinson found that cobra venom has analgesic activity, Brazil(1934 subsequently) find that the venom of C.d.terrificus also has analgesic effect.1940, Steinbroker cobra venom treated 65 routine arthritis and neuralgic patient, and effective percentage is 59%.Two kinds of analgesic Cobroxin made by Hynson, Westco and Dunning company snake venom, are used for treating intractable pain and malignant neoplastic pain; Nyloxin is used for the treatment of arthralgia, and these two kinds of medicines have been put into prescription office of the U.S..Compared with traditional analgesic, the onset of cobra venom analgesic activity is comparatively slow, but have length of holding time, height of tiring, without additive, not tolerific advantage, be the very potential new type analgesic thing of one.
But, because the molecular weight of existing N-GEECDCGSPENPCCD is comparatively large, it is generally acknowledged that impermeable skin enters in patient body, play analgesic activity.Therefore existing Snake bites preparation is mainly injection, so no doubt can ensure its absorbance, but use extremely inconvenient, the risk that untoward reaction occurs is larger.When being particularly applied to the treatment of chronic, intractable pain, need long-term prescription, more inconvenient.
Summary of the invention
The object of the present invention is to provide a kind of naja naja atra analgesic peptide transdermal preparation.
The technical solution used in the present invention is:
Naja naja atra analgesic peptide transdermal preparation, is made up of cobra venom analgesic polypeptide lyophilized powder and adhesive, containing 1 ~ 15% transdermal enhancer in adhesive.
Transdermal enhancer is at least one in azone, Oleum menthae, Borneolum Syntheticum, eucalyptus oil, propylene glycol, glycerol.
Preferably, preparation capable of permeating skin is patch or gel.
The adhesive of patch is water-borne pressure sensitive adhesive, and the adhesive of gel is aqueous gel.
Preferably, water-borne pressure sensitive adhesive consist of azone 0.4 ~ 2 mass parts, Mentholum 3 ~ 8 mass parts, Borneolum Syntheticum 3 ~ 8 mass parts, pressure sensitive adhesive 82 ~ 93.6 mass parts.
Preferably, water-borne pressure sensitive adhesive consist of glycerol 3 ~ 10 mass parts, Oleum menthae 3 ~ 20 mass parts, pressure sensitive adhesive 70 ~ 94 mass parts.
Preferably, the substrate of aqueous gel is glycerol 4 ~ 15 mass parts, sodium carboxymethyl cellulose 2 ~ 10 mass parts.
Preferably, the substrate of aqueous gel is carbomer 0.1 ~ 5 mass parts, propylene glycol 1 ~ 10 mass parts, glycerol 1 ~ 10 mass parts, triethanolamine 0.1 ~ 2 mass parts, azone 0.1 ~ 2 mass parts.
Naja naja atra analgesic peptide transdermal preparation of the present invention, can well Transdermal absorption, and directly can be attached to sore place, long-acting slow-release, analgesic effect is good, safe and reliable, easy to use.
Naja naja atra analgesic peptide transdermal preparation of the present invention, preparation technology is simple, and it is first good by Adhesive only to need, add cobra venom analgesic polypeptide lyophilized powder mix homogeneously again, be coated with afterwards, dry, attachedly serve as a contrast, quality is easy to control, and production cost comparatively injection reduces greatly.
Detailed description of the invention
Naja naja atra analgesic peptide transdermal preparation, is made up of cobra venom analgesic polypeptide lyophilized powder and adhesive, containing 1 ~ 15% transdermal enhancer in adhesive.
Transdermal enhancer is at least one in azone, Oleum menthae, Borneolum Syntheticum, eucalyptus oil, propylene glycol, glycerol.
Preferably, preparation capable of permeating skin is patch or gel.
The adhesive of patch is water-borne pressure sensitive adhesive, and the adhesive of gel is aqueous gel.
Preferably, water-borne pressure sensitive adhesive consist of azone 0.4 ~ 2 mass parts, Mentholum 3 ~ 8 mass parts, Borneolum Syntheticum 3 ~ 8 mass parts, pressure sensitive adhesive 82 ~ 93.6 mass parts.
Preferably, water-borne pressure sensitive adhesive consist of glycerol 3 ~ 10 mass parts, Oleum menthae 3 ~ 20 mass parts, pressure sensitive adhesive 70 ~ 94 mass parts.
Preferably, the substrate of aqueous gel is glycerol 4 ~ 15 mass parts, sodium carboxymethyl cellulose 2 ~ 10 mass parts.
Preferably, the substrate of aqueous gel is carbomer 0.1 ~ 5 mass parts, propylene glycol 1 ~ 10 mass parts, glycerol 1 ~ 10 mass parts, triethanolamine 0.1 ~ 2 mass parts, azone 0.1 ~ 2 mass parts.
Pressure sensitive adhesive is the conventional medicinal pressure sensitive adhesive of aqueous, as polyacrylate water-borne pressure sensitive adhesive, polyamine esters water-borne pressure sensitive adhesive.
During preparation, the substrate of aqueous gel is mixed with suitable quantity of water, adjust its viscosity, obtain adhesive;
Cobra venom analgesic polypeptide lyophilized powder suitable quantity of water is dissolved, mixes with adhesive, stir, coat on back lining materials, dry, cover adherent layer, or directly dry.Preparation technology depends on concrete transdermal agent type.
Its preparation manipulation is substantially identical with the method for conventional preparation capable of permeating skin, is all well-known to those skilled in the art, or is tested by limited number of time namely confirmable.
Below in conjunction with embodiment, further illustrate the present invention.
Embodiment 1
The preparation of transdermal patch mixed glue solution: take glycerol 45g, Oleum menthae 144g, pressure sensitive adhesive 711g, mixs homogeneously glycerol with Oleum menthae, mixes with pressure sensitive adhesive, stirs and get final product.
Preparation: take cobra venom analgesic polypeptide lyophilized powder 0.5g and be dissolved in 10 ml water, mix with mixed glue solution, stir, coat on back lining materials, dry, cover adherent layer, be cut into the paster 1000 of 6cm × 9cm specification, packaging, obtains cobra-venom analgesic polypeptide transdermal patch.
Embodiment 2
The preparation of transdermal patch mixed glue solution: take azone 10g, Mentholum 84g, Borneolum Syntheticum 84g, pressure sensitive adhesive 1680g, is mixed evenly Mentholum, the grinding of Borneolum Syntheticum colloid mill, adds pressure sensitive adhesive and azone, mix homogeneously and get final product.
Preparation: take cobra venom analgesic polypeptide lyophilized powder 0.45g, be dissolved in 10 ml water, mix with mixed glue solution, stir, coat on back lining materials, dry, cover adherent layer, be cut into the paster 1000 of 6cm × 9cm specification, packaging, obtains cobra-venom analgesic polypeptide transdermal patch.
Embodiment 3
The preparation of gel mixed-matrix: take glycerol 50g, sodium carboxymethyl cellulose 30g; By swelling for sodium carboxymethyl cellulose preparation water 900ml, mix homogeneously with glycerol and get final product.
Preparation: take cobra venom analgesic polypeptide lyophilized powder 0.5g, be dissolved in 100ml water, mix with above-mentioned mixed-matrix, stir, subpackage, obtain cobra-venom analgesic polypeptide gel.
Embodiment 4
The preparation of gel mixed-matrix: take carbomer 5g, triethanolamine 5g, propylene glycol 35g, azone .3g, glycerol 30g; By swelling for carbomer suitable quantity of water, stir, add remaining triethanolamine, propylene glycol, glycerol, azone, stir and get final product.
Preparation: take cobra venom analgesic polypeptide lyophilized powder 0.25g, be dissolved in suitable quantity of water, mix with above-mentioned mixed-matrix, adding water to weight is 500g, stirs, subpackage, obtains cobra-venom analgesic polypeptide gel.
the clinical observation of Naja analgesic polypeptide patch treatment lumbar vertebra arthritis ache
1 physical data, with reference to " guideline of clinical investigations of new Chinese medicine treatment osseous arthritis " in " new Chinese medicine guideline of clinical investigations ", is diagnosed as lumbar vertebra osteoarthritis person by x-ray; Age, men and women did not limit at 40 ~ 75 years old; The symptoms such as all cases all kowtow tenderness, movable pain.Adopt completely random comparative study that patient is divided into two groups: matched group and treatment group; Wherein treatment group 30 example, matched group 26 example; Two groups of ages, sex, medical history and severity extents etc. compare there was no significant difference, have comparability.
2 administrated methods
Treatment group adopts Naja analgesic polypeptide paster external application knee joint, and matched group adopts 701 plaster, and every day one pastes.Two groups, during medication, all stop all oral medicine, medicine for external use and other Therapeutic Method.
3 observation index and method
3.1 therapeutic evaluation
Within the 7th, 14,28 day after medication, observe flank pain, tenderness, swelling, the scope of limitation of activity and the improvement situation of situation respectively, and adopt integration method record.
3.2 observational technique
With reference to lumbar vertebra severity of arthritis and the activity index Evaluation Method formulation clinical observation medical history sheet of Lequesne, by designing requirement, unified printing form, when tested front and back and further consultation, according to the contents of a project, records various index, untoward reaction or toxic and side effects.
3.3 severity extent assessments
Pain: sharp ache, is difficult to stand, and affects sleep 3 points; Pain is heavier, can stand, and affects sleep 2 points; Mild pain, can stand, and does not affect sleep 1 point; Without pain 0 point.
X-ray film classification: periarticular and intraarticular many places hyperosteogeny, joint space obviously narrows 3 points; Intraarticular hyperosteogeny is more than 2 places; Joint space does not slightly narrow person 2 points; Intraarticular hyperosteogeny is in 2 sentence, and joint space is without the person of narrowing 1 point.
4 curative effect judging standards
Judge with reference to the criterion of therapeutical effect in " new Chinese medicine guideline of clinical investigations ": effective: sings and symptoms disappears substantially, after treatment, total mark reduces 2/3; Effective: sings and symptoms obviously improves, after treatment, total mark reduces 1/3; Invalid: sings and symptoms is not improved, after treatment, total mark reduces less than 1/3.
5 statistical analysis
Data represent with `x ± s, adopt the analysis of SPSS 13.0 statistical software.The difference of index and data according to the observation, measurement data adopts t inspection, and enumeration data adopts X
2inspection, p<0.05 has statistical significance.
6 results
The analysis of 6.1 liang of group curative effect of medication
Observed result shows, two groups of curative effect of medication are all satisfied, and the obvious effective rate of tested group is 56.7%, and total effective rate is 93.3%; The obvious effective rate of matched group is 46.2%, and total effective rate is 80%.Tested group has significant difference p<0.01 with comparing after treatment of control group, illustrates that aobvious more rate, the total effective rate of tested group are better than matched group.
The two groups of total effective rate analyses of lumbar vertebra arthritis ache treated by table 1
naja analgesic polypeptide paster is to the clinical observation of cervical spondylosis
1 this group of physical data Patients with Cervical Spondylopathy 60 example, man 32 example, female 28 example.Mean age 56.4 scholar 15.1.Incidence shoulder back pain 43 example, upper limb radiated pain 12 example, upper limb and hand anesthesia 37 example, restriction of neck motion 33 example etc.X-ray is taken the photograph sheet and is shown cervical vertebrae physiological flexibility change 36 example, cervical vertebral body and joint hyperplasia 52 example, narrowing of intervertebral space, intervertebral foramina stenosis 28 example.Some patients CT result display intervertebral disc degeneration or outstanding 26 examples.By Ministry of Public Health " new Chinese medicine guideline of clinical investigations.New Chinese medicine treatment cervical spondylosis guideline of clinical investigations " and State Administration of Traditional Chinese Medicine's " disease of tcm Standardization of diagnosis and curative effect " draft diagnostic criteria.
2 administrated methods, in cervical region affected part subsides every day Naja analgesic polypeptide paster, determine the number of medicine used according to pain dimensions, once a day, and continuous 5 days.
3 efficacy evaluations are effective: pain, tenderness disappear, functional rehabilitation; Effective: above-mentioned symptom takes a turn for the better, and function is recovered substantially; Invalid: above-mentioned symptom is still without alleviating, and function has no improvement.
4 statistical analysis
Adopt paired t-test, compare the change of pain index of correlation before and after patient treatment, P<0.05 has statistical significance.
5 results
5.1 according to efficacy assessment standard, and effective patient 28 example, has accounted for and observed 46.7% of case; Effective patient 29 example, accounts for 48.3%; Invalid 3 examples, account for 5%; Total effective rate is 95%.
5.2 these groups of untoward reaction have 2 routine patients to tell local skin burn feeling, and plaster area skin erythema appears in 2 examples, convulsion is itched.Drug withdrawal, after drug withdrawal, above-mentioned symptom is died away.
Total effective rate is analyzed
Naja naja atra analgesic peptide transdermal preparation of the present invention, can well Transdermal absorption, and directly can be attached to sore place, long-acting slow-release, analgesic effect is good, safe and reliable, easy to use.
Naja naja atra analgesic peptide transdermal preparation of the present invention, preparation technology is simple, and it is first good by Adhesive only to need, add cobra venom analgesic polypeptide lyophilized powder mix homogeneously again, be coated with afterwards, dry, attachedly serve as a contrast, quality is easy to control, and production cost comparatively injection reduces greatly.
Claims (1)
1. naja naja atra analgesic peptide transdermal preparation, is made up of cobra venom analgesic polypeptide lyophilized powder and adhesive, and preparation capable of permeating skin is patch or gel, wherein:
The adhesive of patch is water-borne pressure sensitive adhesive, and it consists of: azone 0.4 ~ 2 mass parts, Mentholum 3 ~ 8 mass parts, Borneolum Syntheticum 3 ~ 8 mass parts, pressure sensitive adhesive 82 ~ 93.6 mass parts or glycerol 3 ~ 10 mass parts, Oleum menthae 3 ~ 20 mass parts, pressure sensitive adhesive 70 ~ 94 mass parts;
The adhesive of gel is aqueous gel, and the substrate of aqueous gel is carbomer 0.1 ~ 5 mass parts, propylene glycol 1 ~ 10 mass parts, glycerol 1 ~ 10 mass parts, triethanolamine 0.1 ~ 2 mass parts, azone 0.1 ~ 2 mass parts.
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| CN201010516449.5A CN102451463B (en) | 2010-10-23 | 2010-10-23 | Naja naja atra analgesic peptide transdermal preparation |
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| CN201010516449.5A CN102451463B (en) | 2010-10-23 | 2010-10-23 | Naja naja atra analgesic peptide transdermal preparation |
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| CN102793639A (en) * | 2011-12-16 | 2012-11-28 | 百奥迈科生物技术有限公司 | Plant extract-mediated drug transdermal introducing system and transdermal method thereof |
| CN110201146A (en) * | 2019-07-02 | 2019-09-06 | 南京昂谷医药科技有限公司 | Echidnotoxin gelling agent and preparation method thereof |
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Non-Patent Citations (4)
| Title |
|---|
| 常梅艳 等.应用仿生亲和层析从广东产舟山眼镜蛇(Najanaja atra)蛇毒中分离纯化镇痛多肽.《药物生物技术》.2009,第16卷(第4期),325-329. * |
| 林杰勋.透皮制剂及其释药技术研究进展.《中国药业》.2009,第18卷(第21期),79-80. * |
| 梁映霞 等.广东舟山眼镜蛇蛇毒镇痛活性成分的分离及其药理性质研究.《中药材》.2009,第32卷(第7期),1022-1025. * |
| 王春晓 等.浙江眼镜蛇(Naja naja atra)蛇毒镇痛多肽的分离纯化及其性质的研究.《药物生物技术》.2003,第10卷(第2期),159-164. * |
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