CN109718229B - Anti-inflammatory pharmaceutical composition and application thereof - Google Patents

Anti-inflammatory pharmaceutical composition and application thereof Download PDF

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CN109718229B
CN109718229B CN201910117877.1A CN201910117877A CN109718229B CN 109718229 B CN109718229 B CN 109718229B CN 201910117877 A CN201910117877 A CN 201910117877A CN 109718229 B CN109718229 B CN 109718229B
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cannabidiol
pharmaceutical composition
inflammatory
danshensu
inflammatory pharmaceutical
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CN109718229A (en
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曲桂武
崔明
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Yantai Hemp Biotechnology Co ltd
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Abstract

The invention provides an anti-inflammatory pharmaceutical composition and application thereof, relating to the technical field of medicines, wherein the anti-inflammatory pharmaceutical composition comprises danshensu and cannabidiol; the weight ratio of the danshensu to the cannabidiol is 1 (0.01-100). The research of the invention shows that the danshensu can be used as a solubilizer to improve the dissolution of cannabidiol, and the anti-inflammatory pharmaceutical composition has high water solubility and good rehydration property. Under the weight ratio limited by the invention, the danshensu and the cannabidiol have synergistic interaction, the anti-inflammatory effect is obviously improved, and the cytotoxicity is low. The anti-inflammatory pharmaceutical composition can be applied to preparation of medicines for preventing or treating inflammation, and provides a new way for treating inflammation-related diseases.

Description

Anti-inflammatory pharmaceutical composition and application thereof
Technical Field
The invention relates to the technical field of medicines, in particular to an anti-inflammatory medicinal composition and application thereof.
Background
Inflammation is a common clinical pathological process, and is a complex defense reaction of a living organism having a blood vessel system to an injury factor (such as an allergic reaction generated by bacteria, viruses, antigens, nuclear antibodies, and the like), which can occur in tissues and organs of various parts of the organism. When inflammatory factors act on the body, the body eliminates inflammatory factors through an inflammatory reaction, which is a process of injury and anti-injury. Many common diseases, such as folliculitis, tonsillitis, pneumonia, hepatitis, pancreatitis, nephritis, etc., as well as autoimmune diseases, atherosclerosis, wound repair, etc., belong to the inflammation category. Anti-inflammatory drugs are second only to anti-infective drugs clinically in the 2 nd main category. The medicines capable of eliminating inflammation are collectively called as anti-inflammatory medicines, and can block the generation or release of inflammatory mediators and inhibit inflammatory reaction.
The anti-inflammatory drug mainly comprises non-steroidal anti-inflammatory drug, steroidal anti-inflammatory drug and traditional Chinese medicine. Because the traditional anti-inflammatory drugs have poor selectivity, obvious side effects and great limitation on clinical application, the research and development of novel anti-inflammatory drugs are always the key points of new drug research.
Cannabidiol (CBD) is one of the main chemical components in medicinal plant cannabis sativa, has no addiction, and has important medicinal value in the aspects of tumor resistance, nervous system protection, immunoregulation, inflammation resistance, oxidation resistance and the like. Gb GW pharmaceutical company develops safe (oral mucosal spray for treatment of tuberous sclerosis) and epididolex (for treatment of seizure epilepsy in children) based on CBD. At present, researches show that cannabidiol has potential application prospects in the fields of arthritis, pancreatitis, tumors and the like, but because cannabidiol has poor water solubility, a large amount of cosolvent, excipient and the like are required to be added when the cannabidiol is prepared into a medicament, so that the application of cannabidiol in medicaments is limited.
Danshensu, whose chemical name is D (+) beta- (3, 4-dihydroxyphenyl) lactic acid, is one of the main effective components in Salvia Miltiorrhiza Bge of Labiatae, has protective effect on myocardial ischemia/reperfusion injury, can inhibit platelet aggregation and anticoagulation, has pharmacological actions in various aspects such as anti-inflammation and enhancing organism immunity, and is widely applied clinically as the main component of medicaments for treating various cardiovascular and cerebrovascular diseases at present. Unlike sodium salt, free danshensu is colorless or yellowish oily liquid at normal temperature, has certain liposolubility and solubility in organic solvent, such as methanol and ethanol, higher than that in water.
Disclosure of Invention
The invention provides an anti-inflammatory pharmaceutical composition containing salvianic acid A and cannabidiol in order to overcome the defects of poor water solubility and insufficient anti-inflammatory effect of the existing cannabidiol, the salvianic acid A and the cannabidiol can be synergized under the weight ratio limited by the invention, the anti-inflammatory effect is improved, the cytotoxicity is low, and the salvianic acid A can promote the cannabidiol to be dissolved.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an anti-inflammatory pharmaceutical composition, which comprises danshensu and cannabidiol; the weight ratio of the danshensu to the cannabidiol is 1 (0.01-100).
Preferably, the weight ratio of the danshensu to the cannabidiol is 1 (0.05-20).
Preferably, the dosage form of the composition comprises tablets, capsules, suppositories, oral liquid, dropping pills, powder or injection emulsion.
Preferably, the composition further comprises pharmaceutically acceptable excipients.
The invention also provides application of the anti-inflammatory pharmaceutical composition in the technical scheme in preparation of a medicament for preventing or treating inflammation.
Preferably, the inflammation comprises inflammation caused by pancreatitis, arthritis, gastroenteritis, meningitis, or body surface infection.
Compared with the prior art, the invention has the beneficial effects that:
(1) the research of the invention shows that based on the principle of similar compatibility, the cannabidiol has good solubility in oily danshensu, can form a transparent and uniform solution with high cannabidiol concentration, and the solubility of the cannabidiol in water in the state is larger than that of single cannabidiol, which shows that the danshensu can play a role of a cosolvent for the cannabidiol. As the water solubility test of the embodiment of the present invention, the anti-inflammatory pharmaceutical composition | (lyophilized powder) of the present invention can be dissolved in water to obtain a clear and uniform solution, and the lyophilized powder of the saturated aqueous solution of cannabidiol can be dissolved in water again and can only obtain a milky white solution after being subjected to ultrasonic treatment.
(2) As shown in the embodiment of the invention, when the weight ratio of the salvianic acid A to the cannabidiol is within the range of 1 (0.01-100) defined by the invention, the anti-inflammatory activity of the composition is stronger than that of the salvianic acid A or the cannabidiol at the same mass, and the salvianic acid A and the cannabidiol have positive synergistic effect.
(3) The anti-inflammatory drug composition formed by compounding the salvianic acid A and the cannabidiol has lower cytotoxicity than the cannabidiol under the same quality, and is safer and more reliable.
Drawings
FIG. 1 is a graph showing the effect of the test substance in Experimental example 2 on the release of LPS-stimulated RAW264.7 cytokines NO;
FIG. 2 is a graph showing the effect of the test substance in Experimental example 2 on the release of LPS-stimulated RAW264.7 cell inflammatory factor PGE 2.
Detailed Description
The invention provides an anti-inflammatory pharmaceutical composition, which comprises danshensu and cannabidiol; the weight ratio of the danshensu to the cannabidiol is 1 (0.01-100); preferably 1 (0.05-20).
In the present invention, the dosage form of the composition includes, but is not limited to, tablets, capsules, suppositories, oral liquids, drop pills, powders or emulsion for injection. The present invention is not particularly limited in the manner of preparing the composition into various dosage forms, and the preparation method of the dosage form known in the art may be used.
In the present invention, the composition preferably further comprises pharmaceutically acceptable excipients in addition to the salvianic acid A and the cannabidiol. The pharmaceutical excipients include, but are not limited to, one or more of diluents, fillers, wetting agents, binders, dispersants, thickeners, coating materials, disintegrants, lubricants, antioxidants, preservatives, pH adjusting agents, emulsifiers, isotonicity adjusting agents, and stabilizers.
In the present invention, the diluent and filler include, but are not limited to, one or more of purified water, starch, powdered sugar, dextrin, microcrystalline cellulose, lactose, mannitol, and sorbitol. In the present invention, the wetting agent and binder include, but are not limited to, one or more of distilled water, ethanol, starch slurry, dextrin, sugar powder, syrup, gelatin, acacia gum, polyethylene glycol 4000, sodium carboxymethyl cellulose, ethyl cellulose EC, cellulose derivatives, methyl cellulose MC, hydroxypropyl cellulose HPC, and hydroxypropyl urgent cellulose HPMC. In the present invention, the disintegrant includes, but is not limited to, one or more of dry starch, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, crospovidone, and croscarmellose sodium. In the present invention, the lubricant includes, but is not limited to, one or more of magnesium stearate, aerosil, talc, hydrogenated vegetable oil, polyethylene glycol, and magnesium lauryl sulfate. In the present invention, the emulsifier includes, but is not limited to, one or more of gum arabic, tragacanth, gelatin, phospholipid, apricot gum, cholesterol, potassium stearate, sodium oleate, potassium oleate, sodium lauryl sulfate, calcium stearate, span, brij, fatty alcohol sulfates, and glyceryl stearate.
The invention also provides application of the anti-inflammatory pharmaceutical composition in the technical scheme in preparation of a medicament for preventing or treating inflammation. As shown in the embodiment of the invention, under the same mass, the anti-inflammatory effect of the anti-inflammatory pharmaceutical composition is obviously superior to that of danshensu or cannabidiol, and the anti-inflammatory pharmaceutical composition has a synergistic effect.
The anti-inflammatory composition provided by the invention is generally used for preventing and treating various inflammations. In the present invention, the inflammation includes, but is not limited to, inflammation caused by damage to the immune system or tissues, such as pancreatitis, arthritis, gastroenteritis, meningitis, and inflammation caused by body surface infection.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1 preparation of injectable lyophilized Salvianic acid and cannabidiol
Prescription:
Figure BDA0001970841020000041
the operation is as follows: weighing cannabidiol and salvianic acid A in a prescription amount, adding the cannabidiol into the oily salvianic acid A, and stirring to form a uniform and transparent solution; weighing sodium chloride and mannitol, adding 50% water for injection, stirring to dissolve, adding tanshinol dissolved with cannabidiol, stirring to dissolve, and adding water for injection.
Adding 0.15% by weight of active carbon for injection, stirring for 25 min, filtering for decarbonization, checking intermediates, filtering with 0.22 μm filter membrane for sterilization after qualification, filling the filtrate into a penicillin bottle, freeze-drying to obtain lyophilized powder for injection, inspecting, and packaging.
EXAMPLE 2 preparation of Danshensu + cannabidiol dropping pills
Prescription:
Figure BDA0001970841020000051
the operation is as follows: weighing cannabidiol and salvianic acid A in a prescription amount, adding the cannabidiol into the oily salvianic acid A, and stirring to form a uniform and transparent solution; weighing PEG400, PEG4000, sodium carboxymethyl starch and polyvidone K30 according to the formula, adding into a dripping pill machine for melting at 95 ℃, adding the salvianic acid A dissolved with cannabidiol while stirring, fully and uniformly mixing, wherein the temperature of the medicine material is 85 ℃, the medicine material is dripped into liquid paraffin at a dripping speed of 28 drops/min at a dripping distance of 20cm, condensing at 10 ℃, solidifying to form a dripping pill, taking out and drying to obtain the dripping pill.
EXAMPLE 3 preparation of Salvianic acid A + cannabidiol injection emulsion
Prescription:
Figure BDA0001970841020000052
Figure BDA0001970841020000061
the operation is as follows: weighing cannabidiol and salvianic acid A in a prescription amount, adding the cannabidiol into the oily salvianic acid A, and stirring to form a uniform and transparent solution; weighing glycerol according to the formula amount, adding a proper amount of water for injection, dissolving to prepare a glycerol aqueous solution, and keeping the temperature at 50-60 ℃ to be used as a water phase; weighing phospholipid, poloxamer and soybean oil according to the prescription amount, mixing, stirring and dissolving at 50-70 ℃ to obtain an oil phase; adding oleic acid and danshensu dissolved with cannabidiol into an oil phase, stirring to mix uniformly, adding into a water phase while shearing, shearing at a high speed to form uniform primary emulsion, metering the volume to 5000mL by using water for injection, and passing through a homogenizer to prepare lipid microspheres with uniform particle size and average particle size of 160-280 nm; filtering the obtained liquid with 0.22 μm membrane, introducing nitrogen gas, bottling, and rotary sterilizing with flowing steam at 125 deg.C for 5 min.
Example 4 preparation of Salvianic acid A + cannabidiol Soft capsules
Prescription:
Figure BDA0001970841020000062
the operation is as follows: weighing cannabidiol, salvianic acid A and vitamin E according to the prescription amount, adding the cannabidiol and the vitamin E into the oily salvianic acid A, and stirring to form a uniform and transparent solution; weighing water, glycerol and gelatin according to the prescription amount, uniformly mixing, heating to 60-68 ℃, vacuumizing under 0.04-0.05 Mpa to remove bubbles, and then discharging the gelatin. And (4) after the glue is discharged, injecting the content into the rubber to be encapsulated to obtain a complete capsule, thus obtaining the capsule.
Experimental example 1: effect of Salvianic acid on Water solubility of cannabidiol
1 instruments and reagents
Cannabidiol, self-made, colorless crystals with purity of more than 98% (HPLC); danshensu is self-made, colorless oily liquid with the purity of more than 98 percent (HPLC); acetonitrile (chromatograhy, chemical reagents of national drug group, ltd); lyophilizer (Epsilon 2-4D, Germany), electronic balance (Mettler-Toridol, Germany), high performance liquid chromatography (Thermo Ultimate 3000), Phenomenex Gemini C18 column (5 μ, 250X 4.6mm), detection wavelength 225nm, mobile phase acetonitrile-water (acetonitrile: 72 → 85%). The water used is Wahaha purified water.
2 method of experiment
2.1 saturated concentration investigation
Taking two 10mL volumetric flasks, adding water to the full scale, and slowly adding cannabidiol and cannabidiol respectively according to the weight ratio of 1: 1 is dissolved in danshensu to obtain the composition. The mixture was sonicated while adding until excess, and sonication was continued for 2 hours, during which time the added sample was found to be completely dissolved, and continued until excess. After standing for 1 hour, the supernatant was a saturated solution of the sample. Detecting cannabidiol concentration by high performance liquid chromatography, and determining the influence of danshensu on cannabidiol solubility.
2.2 rehydration experiments
And (3) filling 2.1 parts of saturated solution of cannabidiol and the composition into penicillin bottles, wherein each bottle is 2mL, freeze-drying, observing the appearance of a freeze-dried substance, adding 2mL of purified water, and observing the dissolution condition.
3 results and conclusions of the experiment
At the experimental temperature, the concentration of cannabidiol at saturation in water was 0.46mg/mL, whereas in a saturated solution of the composition, the concentration of cannabidiol was 16.35 mg/mL; in a rehydration experiment, after 2mL of water is added into the freeze-dried powder of the cannabidiol saturated solution, ultrasonic treatment is needed to obtain a milky white solution, and after the water is added into the freeze-dried powder of the composition, slight ultrasonic treatment is carried out to obtain a basically clear colorless solution.
Experimental example 2: anti-inflammatory action research of cannabidiol and salvianic acid A
1 Material
1.1 drugs and reagents
Cannabidiol, self-made, colorless crystals with purity of more than 98% (HPLC); danshensu is self-made, colorless oily liquid with the purity of more than 98 percent (HPLC); mouse mononuclear macrophage RAW264.7, purchased from Shanghai cell biology institute of Chinese academy of sciences; trypsin-EDTA digestive juice, phosphate buffer, fetal bovine serum, and DMEM high-sugar medium (all distributed by Gibco, beijing qian biotechnology limited); DMSO, penicillin and streptomycin (Fluka, distributed by the national pharmaceutical group chemicals beijing ltd); lipopolysaccharide (Aladdin, Shanghai Allatin Biotechnology Ltd.); PGE2ELISA kit (Abnova, distributed by guangzhou new jin biotechnology limited); both the MTT kit (Merck Millipore) and the Griess kit (Abcam) were purchased from New jin Biotechnology, Inc., Guangzhou. Other reagents are analytically pure and are produced by chemical reagents of the national drug group, Inc.
1.2 instruments
SpectraMax iD3 multifunctional microplate reader (Molecular Devices, USA); electronic balance (mettler-toledo instruments (shanghai) ltd); model 101-3A electrothermal blowing dry box (Tester instruments, Inc. of Tianjin); UV-2600 type ultraviolet spectrophotometer (Shimadzu corporation, Japan); thermo Scientific water jacket type CO2Incubator (ThermoFisher Co.).
2 method
2.1 preparation of sample solutions of test substances
The injection emulsion of danshensu, cannabidiol and danshensu plus cannabidiol is prepared according to the auxiliary material prescription in the embodiment 3. Wherein the salvianic acid A is replaced by salvianic acid A with the same weight in the salvianic acid A emulsion, and the cannabidiol A is replaced by cannabidiol A with the same weight in the cannabidiol A emulsion, so as to keep the total weight of the effective components in the three samples the same.
The three emulsions for injection are diluted by DMEM culture solution to a final mass concentration of 50 mug/mL.
2.2 cell culture
Mouse mononuclear macrophage RAW264.7 DMEM culture solution (containing 10% fetal calf serum and 1% penicillin-streptomycin double antibody) at 37 deg.C and 5% CO2Culturing in an incubator, digesting and passaging by using trypsin-EDTA (ethylene diamine tetraacetic acid) liquid when cells grow to 80% of a culture dish in an adherent manner, taking RAW264.7 cells in a logarithmic phase, adjusting the concentration of cell suspension, inoculating a certain volume of the cells into a 96-hole cell culture plate, culturing until the cells grow to the adherent manner, and adding a sample solution. Each set of 5 parallel wells.
2.3 Effect of test Agents on the viability of RAW264.7 cells
Adjusting the cell suspension concentration to 5X 104Inoculating the cells/mL into a 96-well cell culture plate, inoculating 180 mu L of the cells/well, setting a blank control group (replacing a sample solution with DMEM culture solution with the same volume), performing other operations according to the method under 2.2, culturing for 24 hours, adding 20 mu L of MTT solution with the mass concentration of 5mg/mL, and continuing culturing for 4 hours; the culture medium in the wells was aspirated, 150. mu.L DMSO was added to each well, the mixture was shaken for 10min to dissolve the crystals sufficiently, the absorbance value of each well was measured at 490nm (A490nm), and the inhibition rate of the composition on the cells was calculated according to the formula:
cell inhibition ratio (%) (1-administration group A)490nm/blank control group A490nm)×100。
2.4 Effect of test Agents on LPS-stimulated release of RAW264.7 cytokines NO and PGE2
Adjusting the cell suspension concentration to 2X 105one/mL of the cells were inoculated into a 96-well cell culture plate, 1mL of the cells was inoculated into each well, and a blank control group (sample solution was replaced with an equal volume of DMEM medium) and an LPS control group (sample solution was replaced with an equal volume of DMEM medium after 12 hours of treatment with a final concentration of LPS of 1. mu.g/mL).
After the rest of the operations were performed according to the method under item 2.2 and cultured for 12 hours, the supernatant was taken according to the kit instructions, and the release levels of NO and PGE2 in the culture solution were measured by Griess method and ELISA method, respectively.
2.3 statistical treatment
Data was analyzed using IBM SPSS Statistics 25 software. By adopting one-way anova, the difference is significant when P is less than 0.05, and the difference is highly significant when P is less than 0.01.
3 results
3.1 Effect of samples on RAW264.7 cell viability
MTT experiment results show that under the experiment concentration, the inhibition rate of cannabidiol on RAW264.7 cells is slightly higher, 27.46%, and the composition of tanshinol and the two has no obvious influence on cell activity, and the inhibition rate of cells is lower than 20%. See table 1.
TABLE 1 Effect of test substances on RAW264.7 cell viability
Figure BDA0001970841020000091
Figure BDA0001970841020000092
Note: p <0.05 compared to the blank control group.
3.2 Effect of the test Agents on LPS-stimulated RAW264.7 cytokines NO and PGE2 Release
The results are shown in FIGS. 1 and 2. The results show that all three of the test substances significantly inhibited the release of NO from PGE2 (P < 0.01) compared to the LPS control group; under the same mass concentration, the combination of the salvianic acid A and the cannabidiol is superior to the single use of the salvianic acid A and the cannabidiol, and the result has statistical significance (P < 0.05).
The results of the experimental example 1 show that the danshensu has good solubilizing effect on the cannabidiol, and can improve the solubility of the cannabidiol in water by more than 30 times. The results of experimental example 2 show that the anti-inflammatory effect of the composition of salvianic acid A and cannabidiol is better than that of the composition of salvianic acid A and cannabidiol when the salvianic acid A and cannabidiol are used alone at the same mass concentration, and the result shows that the salvianic acid A and cannabidiol can generate positive synergistic effect when used for anti-inflammation.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (4)

1. An anti-inflammatory pharmaceutical composition, comprising salvianic acid A and cannabidiol; the weight ratio of the salvianic acid A to the cannabidiol is 1: 1.
2. an anti-inflammatory pharmaceutical composition as claimed in claim 1, wherein the dosage form of said composition comprises tablet, capsule, suppository, oral liquid, drop pill, powder or emulsion for injection.
3. An anti-inflammatory pharmaceutical composition according to claim 2, wherein said composition further comprises a pharmaceutically acceptable excipient.
4. Use of the anti-inflammatory pharmaceutical composition of any one of claims 1 to 3 in the manufacture of a medicament for the prevention or treatment of inflammation.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107308170A (en) * 2017-07-10 2017-11-03 张斯� Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared
US10716766B2 (en) * 2015-03-02 2020-07-21 Afgin Pharma, Llc Topical regional neuro-affective therapy with cannabinoids

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10716766B2 (en) * 2015-03-02 2020-07-21 Afgin Pharma, Llc Topical regional neuro-affective therapy with cannabinoids
CN107308170A (en) * 2017-07-10 2017-11-03 张斯� Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
丹参素的药理活性与药物动力学研究进展;李骅等;《西北药学杂志》;20110831;第26卷(第4期);第311页 *
四氢大麻酚和大麻二酚的药理研究进展;郭蓉等;《天然产物研究与开发》;20170815;第29卷(第8期);第1451页 *

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