A pharmaceutical composition for treating acute soft tissue injury and application thereof

Abstract

This invention discloses a pharmaceutical composition for treating acute soft tissue injuries. Its active ingredients consist of geniposide and amygdalin in a mass ratio of 1:1-3, preferably 1:2. It can be prepared as a gel or other topical formulation and contains pharmaceutically acceptable excipients. This pharmaceutical composition is developed based on traditional sprain powder. Through the synergistic effect of geniposide and amygdalin, its therapeutic effect is significantly superior to sprain powder and single-component formulations, effectively improving symptoms such as swelling and bruising at the injury site. Its components are clearly defined, and its quality is easily controlled, overcoming the shortcomings of traditional Chinese medicine compound formulas, which are characterized by complex components and inconsistent quality. Furthermore, topical administration causes no gastrointestinal irritation, making it suitable for a wide range of patients and applicable to the preparation of drugs for treating acute soft tissue injuries.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a pharmaceutical composition for treating acute soft tissue injuries, its preparation method, and its application. Background Technology

[0002] Acute soft tissue injury is a common type of trauma in orthopedics, usually caused by direct or indirect force applied to the body, resulting in closed injuries to soft tissues such as muscles, fascia, tendons, or ligaments. This leads to aseptic inflammation and microcirculatory disturbances, causing temporary disruption of the physiological functions of the injured tissues. The clinical manifestations of acute soft tissue injury mainly include local soft tissue swelling, pain, and functional impairment, which can severely affect the patient's quality of life. Currently, the treatment of acute soft tissue injury mainly follows the principles of protection, rest, ice application, compression, and elevation of the affected limb. In terms of drug treatment, nonsteroidal anti-inflammatory drugs (NSAIDs) are the first choice, but oral administration of these drugs carries risks such as gastrointestinal adverse reactions. Topical NSAIDs have a relatively high safety profile, but may increase skin irritation and the risk of allergic reactions, and are not suitable for elderly patients or patients with renal insufficiency; therefore, their potential risks still need to be considered.

[0003] Compared with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), traditional Chinese medicine external therapies are not only safer but also more effective in treating acute soft tissue injuries. Therefore, in-depth research in this area is of great significance. Niu Shang San (Sprain Powder) is a traditional folk remedy for treating external injuries in the Suzhou region with a long history. After modifications (for example, our hospital's prescription improvements to Niu Shang San can be found in CN119185421A), it has been widely used to treat various soft tissue injuries and acute and chronic inflammations, achieving satisfactory results with few adverse reactions. Our previous research has confirmed the effectiveness of Niu Shang San in treating acute ankle sprains.

[0004] However, as a traditional Chinese medicine compound, the chemical composition of Twisted Powder is complex, and the core pharmacological material basis for its efficacy in treating acute soft tissue injuries has not yet been clarified. This not only makes it difficult to accurately establish quality control standards and ensure product quality uniformity, but also limits the in-depth explanation of its pharmacological mechanism and the optimization and upgrading of modern dosage forms. Summary of the Invention

[0005] This invention develops a pharmaceutical composition based on traditional sprain powder, which has a better therapeutic effect on acute soft tissue injuries than sprain powder, and its ingredients are clearly defined and its quality is easy to control.

[0006] In a first aspect, the present invention provides a pharmaceutical composition for treating acute soft tissue injury, the active ingredients of which are composed of geniposide and amygdalin.

[0007] In some embodiments, the mass ratio of geniposide to amygdalin is 1:1-3.

[0008] Preferably, the mass ratio of geniposide to amygdalin is 1:2.

[0009] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0010] In some embodiments, the dosage form of the pharmaceutical composition is an external preparation, including but not limited to gels, creams, ointments, liniments, sprays, patches, tinctures, and film-forming agents.

[0011] Preferably, the dosage form of the pharmaceutical composition is a gel.

[0012] In a second aspect, the present invention provides the use of the pharmaceutical composition described in the first aspect in the preparation of a drug for treating acute soft tissue injuries.

[0013] Beneficial effects

[0014] (1) The combination of geniposide and amygdalin has a synergistic effect, and the therapeutic effect on acute soft tissue injuries is significantly better than that of the traditional Sprained Injury Powder compound prescription.

[0015] (2) Through formula screening, the optimal mass ratio of geniposide to amygdalin was obtained, achieving the maximization of drug efficacy.

[0016] (3) It avoids the complex components of traditional Chinese medicine compound prescriptions, clarifies the combination of single active ingredients, and it is easy to accurately establish quality standards, solving the technical defects of uneven quality and unstable efficacy of the original compound prescription.

[0017] (4) It removes non-pharmacodynamic impurity components in the compound prescription; local external administration has no gastrointestinal irritation of oral drugs, and is applicable to a wider range of people. Specific embodiments

[0018] The following specific examples are used to further illustrate the present invention, but these examples should not be construed as limiting the present invention.

[0019] Example 1: Study on the therapeutic effect on rats with acute soft tissue injury model

[0020] Taking rats with acute soft tissue injury model as the experimental object, the differences in the specific therapeutic effects between the single active ingredient and its combination in Sprained Injury Powder and Sprained Injury Powder were studied.

[0021] 1. Experimental animals

[0022] 72 SPF-grade male SD rats at 8 weeks of age, with a body weight of (220 ± 10) g, were provided by Shanghai Jihui Experimental Animal Breeding Co., Ltd., and the animal production license number: SCXK (Shanghai) 2022-0009.

[0023] 2. Experimental drugs

[0024] (1) Sprain Powder:

[0025] All medicinal materials were purchased from Suzhou Tianling Chinese Medicine Pieces Co., Ltd. The composition of the medicine is as follows: 20g of gardenia, 10g of peach kernel, 10g of safflower, 10g of Panax notoginseng powder, 20g of Angelica sinensis tail, 20g of costus root, and 10g of Lepidium apetalum. The above medicines are ground into fine powder, then white petrolatum is added and heated to melt, and then mixed evenly to form a paste for later use.

[0026] (2) Gardenin gel (per 100g):

[0027] Table 1: Gel Ingredient Composition

[0028]

[0029] preparation:

[0030] Matrix swelling: Sprinkle carbomer into 40 mL of purified water, let it stand for 12 h to swell, and stir until a uniform colloid without particles is formed.

[0031] Dissolving the main drug: Add glycerin and propylene glycol to the remaining purified water, then add geniposide while stirring, and stir at room temperature until completely dissolved;

[0032] Mixing ingredients: Add the active pharmaceutical ingredient solution to the carbomer colloid and stir until homogeneous; add azone and ethylparaben and continue stirring until homogeneous;

[0033] pH adjustment and shaping: Slowly add triethanolamine to adjust the pH of the system to 6.5, and stir until a transparent, viscous, uniform gel is formed;

[0034] Defoaming and filling: Vacuum defoaming is performed to remove air bubbles, and the product is aseptically filled into an external medication applicator.

[0035] (3) Amygdalin gel:

[0036] Compared to geniposide gel, the difference is that 1g of amygdalin is used instead of 1g of geniposide, while the rest of the composition and preparation are the same as geniposide gel.

[0037] (4) Gardenoside / Amygdalin Compound Gel Formula 1 (1:1):

[0038] Compared to geniposide gel, the difference lies in the active ingredients being 0.5g geniposide + 0.5g amygdalin, while the rest of the composition and preparation are the same as geniposide gel.

[0039] (5) Gardenoside / Amygdalin Compound Gel Formula 2 (1:2):

[0040] Compared to geniposide gel, the difference lies in the active ingredients being 0.33g geniposide + 0.67g amygdalin, while the remaining composition and preparation are the same as geniposide gel.

[0041] (6) Gardenoside / Amygdalin Compound Gel Formula 3 (1:3):

[0042] Compared to geniposide gel, the difference lies in the active ingredients being 0.25g geniposide + 0.75g amygdalin, while the remaining composition and preparation are the same as geniposide gel.

[0043] 3. Animal grouping, modeling, and intervention

[0044] 3.1 Grouping Method

[0045] Seventy-two rats were weighed, sorted by weight, and numbered. Seventy-two consecutive random numbers were selected from a random number table and recorded below the rat number. All random numbers were sorted from smallest to largest. Rats sorted as 1-9, 10-18, 19-27, 28-36, 37-45, 46-54, 55-63, and 64-72 were respectively assigned to the blank group, model group, sprain powder group, geniposide gel group, amygdalin gel group, geniposide / amygdalin compound gel prescription group 1, geniposide / amygdalin compound gel prescription group 2, and geniposide / amygdalin compound gel prescription group 3.

[0046] 3.2 Modeling Method

[0047] All rats were acclimatized for 7 days. The control group rats underwent only hair removal and anesthesia, without modeling, while the other 7 groups underwent modeling. Rats were fasted for 12 hours prior to modeling but allowed free access to water. Inhalation anesthesia was administered using isoflurane. Hair was first shaved from the right hind leg thigh of the rat, then residual hair was removed with a 6% sodium sulfide solution, and the mid-section of the rectus femoris muscle on the right hind leg thigh was marked as the impact point. The rat was fixed in a prone position on a rat board, with the right hind leg slightly externally rotated to fully expose the marking point. Gauze was placed under the marking point to prevent fracture due to suspension during impact. A 20cm long plastic tube was vertically fixed above the marking point, and a 250g iron ball was dropped from the top of the tube, causing it to hit the rat's marking point with a contact area of ​​approximately 1cm². 2 The procedure was repeated 6 times. After modeling, the rats showed swelling and ecchymosis at the injury site, and lameness in the right hind limb. Physical examination confirmed no abnormalities such as joint dislocation, fracture, or skin damage, indicating that the modeling was successful.

[0048] 3.3 Intervention methods

[0049] After model establishment, medication was administered starting the following day. In the sprain powder group, the sprain powder was applied topically to the right posterior thigh of the rats. In the geniposide gel group, the amygdalin gel group, the geniposide / amygdalin compound gel prescription 1 group, the geniposide / amygdalin compound gel prescription 2 group, and the geniposide / amygdalin compound gel prescription 3 group, the powder was applied to the same site, with a thickness of approximately 1 mm in each group. After administration, the area was covered with two layers of gauze and bandaged to prevent the rats from consuming the powder. The dressing was changed once daily for one week. The control group and the model group received no treatment.

[0050] 3.4 Assessment of limb injury in rats

[0051] Damage should be scored according to the following criteria:

[0052] Table 2: Scoring Criteria for Limb Injuries

[0053]

[0054] The higher the total score, the more severe the injury to the affected limb.

[0055] 3.5 Statistical analysis of limb injury scores

[0056] The injury scores of the injured limbs of rats in each group were assessed on days 1, 3, 5, and 7 of the experiment. The specific results are as follows:

[0057] Table 3: Limb injury scores of rats in each group at different time points after intervention

[0058]

[0059] † This indicates that compared to the control group, p < 0.05. †† This indicates that p < 0.01 compared to the control group;

[0060] * This indicates that compared to the model group, p < 0.05. ** This indicates that p < 0.01 compared to the model group;

[0061] # This indicates that compared to the sprain relief group, p<0.05. ## This indicates that p < 0.01 compared to the sprain powder group;

[0062] △ This indicates that compared to the geniposide / amygdalin compound gel prescription, the two groups showed p<0.05. △△ This indicates that compared to the geniposide / amygdalin compound gel prescription, the two groups showed p<0.01.

[0063] Compared with the control group, the injury scores of the injured limbs in the model group were significantly higher at all time points (††P<0.01), indicating that the acute soft tissue injury model was successfully established. After intervention, the scores of the sprain powder group, geniposide gel group, and amygdalin gel group were all significantly lower than those in the model group ( ** P < 0.01, and there was no statistically significant difference among the three groups (P > 0.05), indicating that the efficacy of the three treatments was comparable. Compared with the geniposide gel group and the amygdalin gel group, the scores of all prescription groups of the compound gel were further reduced (trend analysis), and were also significantly lower than those of the sprain powder group. ##P < 0.01); among them, compound prescription group 2 had the lowest score, and was significantly better than compound prescription group 1 and group 3 at all time points (P < 0.01). △△ P < 0.01, indicating that the compound prescription has a synergistic effect, and prescription group 2 is the optimal solution.

[0064] Finally, it should be noted that the above examples are merely specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments and many variations are possible. All variations that can be directly derived or conceived by those skilled in the art from the disclosure of this invention should be considered within the scope of protection of this invention.

Claims

1. A pharmaceutical composition for treating acute soft tissue injury, characterized in that, The active ingredients of the pharmaceutical composition consist of geniposide and amygdalin.

2. The pharmaceutical composition according to claim 1, characterized in that, The mass ratio of geniposide and amygdalin is 1:1-3.

3. The pharmaceutical composition according to claim 2, characterized in that, The mass ratio of geniposide and amygdalin is 1:

2.

4. The pharmaceutical composition according to any one of claims 1-3, characterized in that, The pharmaceutical composition also includes pharmaceutically acceptable excipients.

5. The pharmaceutical composition according to any one of claims 1-4, characterized in that, The dosage form of the pharmaceutical composition is a topical preparation.

6. The pharmaceutical composition according to claim 5, characterized in that, The dosage form of the pharmaceutical composition is a gel, cream, ointment, liniment, spray, patch, tincture, or film.

7. The pharmaceutical composition according to claim 6, characterized in that, The dosage form of the pharmaceutical composition is a gel.

8. Use of the pharmaceutical composition according to any one of claims 1-7 in the preparation of a medicament for treating acute soft tissue injury.

Images