WO2004103264A2

WO2004103264A2 - Hemostatic antibacterial composition and products incorporating the same

Info

Publication number: WO2004103264A2
Application number: PCT/IN2004/000141
Authority: WO
Inventors: Mini Thomas; Ajit Sitaram Manke; Alain Khaiat; William Hart
Original assignee: Johnson & Johnson Limited
Priority date: 2003-05-22
Filing date: 2004-05-21
Publication date: 2004-12-02
Also published as: WO2004103264A3; CN1548167A; CN1241651C

Abstract

This invention relates to a hemostatic antibacterial composition which comprises an extract of cephalanoplos segetum and benzalkonium chloride. Preferably a local anesthetic and a surfactant are added to this composition. This synergistic composition decreases blood coagulating time considerably. Local anesthetic used may be licodine hydrochloride. Medicament containing strips, pouches and compresses are included in this invention. Method of making this synergistic composition is by admixing the components under stirring. Medicament containing cotton or non-woven strips with the composition and making the desired products therewith.

Description

"HEMOSTATIC ANTIBACTERIAL COMPOSITION AND PRODUCTS INCORPORATING THE SAME"

TECHNICAL FIELD OF THE INVENTION:

This invention relates to hemostatic antibacterial composition which contains an extract of Cephalonoplos segetum and benzalkonium chloride. This composition exhibits synergy and decreases blood clotting time considerably even in small doses. Optionally, known local aneastetic compounds such as licodane hydrochloride surfactants, binders and the like may be added to the composition. Products incorporating this composition may be bandages, band aid type of stickers and the like. Shortening of co-agulation time is observed even when very small quantity of the extract is added to known compositions of benzalkonium compound and local anaesthetic compounds.

BACKGROUND ART:

Cephalonoplos segetum commonly known as Field Thistle or Xiaoje in Chinese language is a prickly composite plant widely available.

An extract of this plant is reported to have hemostatic, properties. Pharmacopoea of the Peoples Republic of China - English edition 1992, page 94 reports application of fresh herb topically after pounding it. Application of fresh herb no doubt is messy, inconvenient and cumbersome. More than that, availability of fresh plant, when required cannot be assured. Benzalkonium chloride is a known and reported topical antiseptic (The Merck Index, 11 Edition 1989) Antiseptic bandages commercially known as 'Bandaids' of Johnson and Johnson, India contains 0.1% to 0.5% of benzalkonium chloride.

OBJECTS OF THIS INVENTION:

The main object of this invention has been to develop a composition which has reduced co-agulation time or better hemostatic action than the hitherto known hemostatic compounds or composition. A composition with improved hemostatic properties and efficacy is produced by combining benzalkonium chloride and an ethyl alcohol/water extract of cephalanoplos segetum. Enhanced hemostatic efficacy is also shown by the application of this composition on a suitable physical matrix. The composition of this invention may optionally contain known local anesthetic compounds surfactants and binders/carriers.

Hemostatic anticeptic composition of this invention may preferably have 1 to 30.61% by weight of ethyl alcohol/water extract of cephalonoplos selgetum and 0.1 to 0.5% by weight of benzalkonium chloride. This composition may optionally contain 1 - 2% by weight of a local anaesthetic and/or 0.1 to 0.5% by weight of a known surfactant.

A compress consisting of compressed or raised cotton or a non-woven strip or band soaked in a composition described herein above is also one of the objects of this invention. The composition in this case may preferably have 1 to 5.0% by weight of cephalanoplos segetum extract and 0.1 to 0.5% by weight of benzalkonium chloride optionally with 1 to 2% by weight of a local anesthetic and/or 0.1 top 0.5% by weight of surfactants sealed in a pouch or sachet. According to another embodiment of this invention, a bandage comprising a cotton or non-woven strip impregnated with a composition containing an extract of cephalonoplos segetum, benzalkonium chloride, a known local anesthetic compound and surfactant and dried thereafter is provided.

According to yet another embodiment, the bandage impregnated and dried with the composition of this invention may be provided with a backing having breathing perforation. This backing may have an adhesive coating at the inner surface thereof. A medicated strip incorporating the composition of the subject invention may be bonded on to the inner surface of this backing layer. A non-stick cover is provided over this medicated strip. A feel of strip is provided over the non-stick cover and is stuck to the inner surface of the backing layer.

In all the above modifications, the composition may have 1.55% to 30.61% by weight of cephalonoplos segetum extract and 0.13% to 0.18% by weight of benzalkonium chloride in any known and pharmaceutically acceptable solvent.

A method of preparing a hemostatic antibacterial composition consisting addition and dissolution of an alcoholic/water extract of cephalanoplos segetum in powder form with benzalkonium chloride, a local anesthetic and surfactants in a pharmaceutically acceptable solvent forms a part of this invention.

A method of producing a compress in the form of a pouch or sachet containing the hemostatic antibacterial composition of this invention also is a part of this invention. A raised cotton or a non-woven strip is soaked in the composition of this invention and the sealed strip is sealed in a pouch or sachet to provide this compress. SUMMARY OF THE INVENTION

This invention relates to a hemostatic antibacterial composition which comprises an extract of cephalonoplos segetum and benzalkonium chloride.

The composition according to this invention contains 1 to 30.61% by weight of cephalonoplos segetum extract and 0.1 to 0.5% by weight of benzalkonium chloride.

The composition may optionally contain local anesthetic and surfactants.

Preferred extract is an ethanol/water extract of the plant and the local anesthetic is lidocaine hydrochloride. Preferably 1 to 2% by weight of local anesthetic compound and 0.1 to 0.5% by weight of the surfactant is used in a solvent.

This invention also relates to a method of making hemostatic antibacterial products such as a bandage, compress and the like which comprises the steps of incorporating the hemostatic antibacterial composition as described hereinabove by soaking raised cotton or a non-woven strip in the composition sealing the soaked strip in the form of a bandage or compress in a known manner.

BRIEF DESCRIPTION OF THE INVENTION WITH REFERENCE TO PREFERRED EMBODIMENTS

A tincture obtained by cold water/ethyl alcohol extract of cephalonoplos segetum (Please clarify if ethyl alcohol water admixture is used for this extraction or is the extraction carried out separately) is prepared. 1 ml of this tincture is found to be equivalent to 5 g of crude plant extract. This tincture was tested separately to ascertain its wound heating and hemostatic properties. Test were carried out to assess the hemostatic efficacy of benzalkonium chloride separately. Further, a composition of benzalkonium chloride and the plant extract was tested for its properties. These studies clearly established that addition of cephalonoplos extract clearly reduces the coagulation time as compared to the tincture and benzalkonium chloride separately.

In a preferred embodiment range of the components in the composition are as follows:

1. 1.55% to 30.61% by weight of cephalonoplos segetum extract

2. 0.13 to 0.18% by weight of benzalkonium chloride

3. about 2% by weight of lidocaine hydrochlordie and

4. 0.1 to 0.5% by weight of a known surfactant.

The extract specified under (1) may be in the tincture form or powder form.

The bandage containing hemostatic antibacterial composition according to this invention is made by

(a) impregnating raised cotton or non-woven strip with a composition of 1 to 12 gm of cephalonoplos segetum extract powder and 0.05 to 0.2 gm of 50% solution of benzalkonium chloride in a pharmaceutically acceptable solvent such that the percentage weight pick up or add-on weight of the medicament on the strip is 180 to 520% for benzalkonium chloride and 155 to 255% for cephalonoplos segetum and

(b) drying the medicated strip at 50 to 110°C to remove the solvent. In another embodiment the bandage obtained herein above is subjected to further steps of:

(a) bonding the medicated strip on to the inner surface of a backing layer provided with breathing perforation having a coat of adhesive thereon,

(b) providing a non-stick cover over said medicated strip and

(c) providing one or more peel off strips over said non-stick cover and the peel of strips being held to the inner surface of the backing layer.

The medicament strip impregnated with the composition may be sealed in a pouch or sachet which preferably is made of aluminium film or foil.

The solvents used in preparing the composition may be water, ethyl alcohol propanol or ethyl acetate and the local anesthetic may be lidocained hydrochloride or benzocaine hydrochloride.

The surfactants used in this invention may preferably be polyethylene glycol and 40 hydrogenated castor oil. The backing paper may be cotton cloth, an non- woven fabric made from polyvinyl chloride, polyurethane, polyethylene, ethylene vinyl acetate or such non-woven fabric.

Peel-off strips may be made of siliconised paper or high density polyethylene.

DESCRIPTION WITH REFERENCE TO EXAMPLES AND COMPARATIVE STUDY REPORTS:

The following examples are illustrative of the invention and is not intended to the limitative: EXAMPLE 1

A hemostatic antibacterial solution was obtained by mixing under stirring cephalonoplos segetum extract powder (1 gm), benzalkonium chloride (0.2 gm of 50% benzalkonium chloride), sodium chloride (0.61 gm) and lidocaine hydrochloride (2 gm) with purified water (96.19 gms).

EXAMPLE 2

A solution was obtained by the procedure of Example 1 using 97.19 gms of purified water without cephalonoplos segetum extract powder.

EXAMPLE 3

A hemostatic antibacterial solution was obtained by mixing under stirring cephalonoplos segetum extract powder (1 gm), benzalkonium chloride (0.2 gms of 50% benzalkonium chloride), sodium chloride (0.61 gms lidocaine hydrochloride (2 gm) and cremaphor RH40 (0.6 gm) with purified water (95.59 gms).

EXAMPLE 4

A solution was obtained by the procedure of Example 1 using 96.59 gms of purified water without cephalonoplos segetum extract powder.

EXAMPLE 5

Compresses were made by soaking non-woven strips in the solution of Examples 1 to 4 and sealing them in aluminium foil. Comparative coagulation Time studies using Platelet Rich and Platelet Poor Plasma fractions were carried out with the solutions of Examples 1 to 4 and the respective compresses and the results were as shown in the following Table 1.

Table 1

EXAMPLE 6

Non-woven cotton cloth was impregnated with a solution of cephalonoplos segetum extract powder (1kg) and benzalkonium chloride (0.05 kg of 50% benzalkonium chloride) in 98.95 kg purified water in the impregnation system of Fig 1. The percentage weight pick-up or add-on weight of the actives on the cloth was 520% for benzalkonium chloride and 163% for cephalonoplos segetum and the medicated cloth was dried in ovens at 110°C. The dried medicated cloth was cut to the required sizes. Each medicated strip was found to contain 1.76% w/w of the actives.

The medicated strips may be used as such as bandages in which case they are tied around the affected area or fixed on the affected area with the help of adhesive coated tapes. Alternatively, the medicated strips may be formed into bandages as shown in Fig 2 of the accompanying drawings, in which the medicated strip is marked 12. 13 is a backing layer provided with breathing perforations 14 and coated with an adhesive (not shown) on its inner surface. The medicated strip is bonded onto the inner surface of the backing layer. 15 is a perforated non-stick cover provided over the medicated strip and fixed to the inner surface of the backing layer. 16a and 16b are peel-off strips provided over the non-stick cover and fixed to the inner surface of the backing layer.

Comparative coagulation time studies were carried out using typical bandages (medicated strips) of Example 6 and the findings were as given in the following Table 2:

Table 2

The cephalonoplos extract powder used in the above experiments was obtained from Tianjiang Pharmaceutical Co Ltd, China.

In both the above Tables coagulation time > 15' means no coagulation activity.

Table 1 shows that solutions with cephalonos extract powder (ie Examples 1 and 3) and respective compresses demonstrated coagulation whereas those without cephalonoplos extract powder (ie Examples 2 and 4 and the respective compresses) did not demonstrate coagulation. Table 2 shows that non-woven cotton cloth impregnated wit cephalonoplos extract powder of 2.37% by weight demonstrates coagulation against platelet rich plasma i.e., coagulation by platelet aggregation but does not demostrate coagulation against platelet poor plasma. This means that it has no effect on the factors responsible for the coagulation cascade i.e., final clotting. Non-woven cloth impregnated with cephalonoplos extract powders at higher percentages of 4.6%, 7.5% and 19.6% demostrate coagulation activity both against platelet rich and platelet poor plasmas. Non-woven cotton cloth impregnated with water and non-woven cloth by itself do not have any blood coagulating activity both against platelet rich and platelet poor plasmas. Non-woven cloth impregnated with benzalkonium chloride of 0.1% has certain blood coagulation activity against platelet rich plasmas but no coagulation activity against platelet poor plasma. The bandage of Example 6 of the invention comprising 1.76% w/w percent of cephalonoplos extract powder and benzalkonium chloride shows coagulation activity against platelet rich as well as platelet poor plasmas demonstrating that when both are used in combination even at as low a concentration as 1.76% w/w there is synergistic activity on platelet aggregation as well as the coagulation cascade as against the lowest concentration of 2.37% w/w of cephalonoplos extract powder alone.

Antimicrobial efficacy study of the bandages of Example 6 was carried out as follows:

Samples of non-woven cotton cloth and bandage of Example 6 of sizes approx. 15 x 15 mm were placed on24 hrs old cultures of E.coil ATCC 8739, Staph aureus ATCC 6538, Ps Aeruginosa ATCC 9027 and C Albicans ATCC 10231. After a period of 48 hours it was observed as follows:

An inhibition zone of 15 mm x 15 mm was formed by the bandage of Example on the Staph aureus culture thereby demonstrating its activity against this bacteria.

Claims

CLAIMS:

1. A hemostatic antibacterial composition which comprises an extract of cephalonoplos segetum and benzalkonium chloride in a pharmaceutically acceptable solvent.

2. The composition as claimed in claim 1 containing a local anesthetic selected from lidocaine hydrochloride or benzocaine hydrochloride.

3. The composition as claimed in claim 1 containing pharmaceutical surfactants and binders.

4. The composition as claimed in claims 1 to 3, which comprises 1 to 30.61% by weight of cephalonoplos segetum extract and 0.1 to 0.5% by weight of benzalkonium chloride, said . composition optionally containing 1 to 2% by weight of a local anesthetic and for 0.1 to 0.5% by weight of a known surfactant.

5. The composition as claimed in claims 2 to 4 wherein the local anesthetic is lidocaine hydrochloride.

6. The composition as claimed in claims 1 to 5, wherein cephalonoplos segetum extract is an ethyl alcohol/water extract preferably dried to a powder form.

7. A hemostatic antibacterial product such as a bandage or compress which comprises a composition containin gan extract of cephalonoplos segetum and benzalkonium chloride mounted on a physical matrix.

8. The hemostatic antibacterial product as claimed in claim 6 wherein said bandage is a cotton or non-woven strip impregnated with said extract and is mounted on a physical matrix.

9. The hemostatic antibacterial product as claimed in claims 6 and 7 wherein said composition has 1 to 30.61% by weight of cephanoplos segetum extract and 0.1 to 0.5% by weight of benzalkonium chloride said composition optionally containing 1 to 2% by weight of a local anesthetic and/or 0.1 to 0.5% by weight of a known surfactant.

10. The product as claimed in claims 6 to 8 wherein said physical matrix is a cotton strip or a non-woven synthetic fabric having breath perforations at its base.

11. The product as claimed in claims 6 to 9 wherein said cephanoplos segetum extract is an ethyl alcohol/water extract.

12. The product as claimed in claims 6 to 11 wherein said cotton strip or non- woven fabric having the composition incorporated therein is dried before fixing on the physical matric and is then covered with a protective seal and perforated strips.

13. A method of preparing a hemostatic antibacterial composition comprising the step of addition and dissolution of an extract of cephalanoplos segetum in powder from with benzalkonium chloride, preferably with a local anesthetic and/or a surfactant in a pharmaceutically acceptable salt solvent.

14. The method as claimed in claim 12 wherein said cephalonoplos extract is an ethyl alcohol/water extract, preferably in powder form.

15. The method as claimed in claims 12 and 13 whrien 1 to 30.61% by weight of cephalonoplos segetum extract and 0.1 to 0.5% by weight of benzalkonium chloride is added to a pharmaceutically acceptable solvent under stirring optimally in the presence of 0.1 to 0.5% by weight of lidocaine hydrochloride and 0.1 to 0.5% by weight of a known surfactant.

16. A method of preparing a bandage compress, medicament strip or the like which comprises the steps of impregnating a raised cotton or non-woven strip with a composition of 1 to 12 gm of cephalonoplos seetum extract powder and 0.05 to 0.2 gm of a 50% solution of benzalkonium chloride in a pharmaceutically acceptable solvent, and drying said impregnated strip at 50 to 110°C to remove the solvent.

17. The method as claimed in claim 16 wherein said medicated strip is bonded to the inner surface of a backing provided with breathing perforations having an adhesive coating, providing a non-stick cover to said medicated strip and providing one or more peel off strips to said non-stick cover.

18. A method as claimed in claim 16 wherein said impregnated cotton is sealed in a pouch or sachet.

19. Use of hemostatic, antibacterial composition which comprises an extract of cephalonoplos segetum and benzalkonium chloride preferably containing a local anesthetic and a surfactant as wound cleansing, antibacterial and coagulation enhancing agent.