GB2156214A - Topical transfer factor compositions - Google Patents

Abstract

A composition for treatment of skin lesions, blemishes, acne, herpes simplex or condyloma contains transfer factor in a carrier, e.g. a non-toxic byophilic base.

Description

SPECIFICATION Transfer factor composition and skin treatment This invention relates generally to a topical composition, and more particularly to atopical composition including transfer factor.

Herpessimplexvirustype 1 causesmucocutaneous lesions around the mouth. The type 2 virus, which has been shown to be venereal transmitted, causes lesions in the genital area. Various treatments have been proposed and the viruses have resisted the various treatments. Recent proposals include the use of various synthetic acyclic purine nucleosides as in U.S. Patent No. 4,199,574. Another proposal appears in Kahn, A. et al.: Transfer Factor in the Treatment of Herpes Simplex Types 1 and 2, Dermatologica 163: 177-185(1981) which suggests that injections of transfer factor may be helpful in controlling recurrent herpes simplex. Notwithstanding these reported improvements, it is desirable to treat the infections by applying topical composition.

Treatment of herpes simplex, condyloma, acne and otherskin lesions by way of application of a topical composition in the form of a cream or ointment is preferred to parenteral administration as a topical composition may be applied convenientlywithoutthe necessity of a physician visit. Additionally, topical application permits application ofthe active ingredients directly to the lesion and the surrounding area as required. Significantly, application of a topical composition avoids parenteral injection, thus minimizing foreign protein exposure to the patient. Accordingly, itwoule be desirable to provide an improved topical composition effective in the treatment of skin lesions, such as skin blemishes, herpes simplex condyloma and the like.

Generally speaking, in accordance with the invention, a tppical composition including transferfactorfor dermatological useis provided.Thetopical composi- tion in accordance with the invention includes a non-toxicvehicle andtransferfactor and may include an enhancing penetrant dispersed therein. Atypical composition in accordance with the invention includes between about 1 and 10 Units oftransferfactor per gram of total composition and may contain between 0 to 15 percent by weight of a penetrant, such as dimethyl sulfoxide (DMSO) or low molecular weight dextran. The skin lesions are treated by applying the topical composition to the infected area between three and five applications per day. A 30 gram sample is sufficient for about 21 days of treatment.

Accordingly, it is an object of the invention to provide an improved topical composition for dermatological use.

Still other objects and advantages of the invention will in part be obvious and will in part be apparent from the specification.

The invention accordingly comprises the several steps and the relation of one or more of such steps with respect to each of the others, and the composition possessing the features, properties, and the relation of constituents, which are exemplified in the following detailed disclosure, and the scope of the invention will be indicated in the claims.

The topical composition prepared in accordance with the invention includes transferfactor in a gentle vehicle. The vehicle is preferably a gentle, non-toxic carrier and may be an unscented moisturizing formula generally used for dry skin care. The preferred composition includes an enhancing penetrant, such as dimethyl sulfoxide or low molecular weight dextran for increasing penetration of the transfer factor into the skin.

Transfer factor is obtained from the lymphocytes of a donar having no history of recurrent infection by herpes virus. It is believed to be a low molecular weight (5,000-10,000) dialysable protein made up of amino acids with RNA base. The transfer factor may be prepared as documented in the medical literature.

For example, detailed preparation of transferfactor is described in Warren S.: Transfer Factorforthe Practicing Allergist- Immunologist, Annals of Allergy, 39130132 (August 1977). The procedure I described therein for production of crudetransferfactor is set forth asfollows for convenience: 1. Obtain a heparinized whole blood sample from a suitable donor. About 48 ml is required (4 green top vacutainers).

2. Transferthe well mixed blood to a clear 50 ml cylinder. Cover and allow to stand at room temperaturn to settle for a bout two hours.

3. Prepare a clear 50 ml syringe by removing the plunger and loosely stuffing the barrel with clear cotton wool and sealing the meedle outlet with a cover.

4. Carefully, using a transfer pipet, transfer the plasma and buffy coat layer fro the cylinder into the prepared syringe so that the plasma is soaked up by the cotton wool and no free liquid is in the syringe.

5. Carefully replace the plunger into the syringe barrel without compressing any of the plasma satu rated cotton wool. Incubate the syringe and contents for 20 minutes at 37"C.

6. Open the needle outlets and compress the cotton wool so as to express the lymphocyte-rich plasma completely into a clear centrifuge tube.

Discard the cotton wool.

7. Remove a small quantity of this cell suspension for determining the absolute cell count. (Thetotal cell countofthe suspension).

8. Gently centrifugethe cell suspension for 15 minutes and then decantthe plasma without disturb ing the cell button at the bottom of the centrifugetube.

9. Wash the cells three times with about 25 ml of 0.5N saline. Each time disperse the cells in the wash fluid thoroughly, centrifuge and discard the wash solution.

10. Reconstitutethecell suspension byadding sufficient normal saline so that 1 mlofthefinal solution will contain 108 cells as a concentration. (108 This print takes account of replacement documents submitted after the date of filing to enable the application to comply with the formal requirements of the Patents Rules 1982.

ceils/mi).

11. Stopperthetube and alternately freeze and thaw the suspension a total of five times.

12. Afterthefinal thaw centrifugethe disrupted cell suspension at 2500 RPM for 15 minutes.

13. Decantthesupernatantfluid into a syringe fitted with a sterile millipore filter.

14. Expressthefluid through the milliporefilter into sterile vials oraliquots using aseptictechnique.

15. Retain one aliquotfor sterility testing and potency testing, and store the balance in the freezer for later use. Thisfinal solution represents crude transferfactor extract.

The final solution prepared in the above manner contains approximately 1 Unit of transferfactor per millilitre of solution. (Defined as 1 Unit = 108 cells) The transferfactortopical composition is prepared by mixing thetransferfactor in a vehicle so thatthe transferfactor is present in a concentration of about 1 Unit per gram ofcomposition.The preferred composition may also include up to about 15 weight percent of an enhancing penetrant, such as DMSO or low molecularweight dextran. It is most preferred that about 5% by weight of DMSO be used as human test indicatethatthere is no effect from the DMSO at this concentration as it penetrates. A low molecular weight dextran of about4,000 daltons can be substi tuted forthe DMSO.When the dextran is utilzed,the same percent by weight is preferably included.

During treatment with the transfer factor, the composition is applied to the infected area aboutfour times per day. A 30 gram sample is sufficientfor about 21 days of treatment. Thus, a patient applies about 30 Units oftransferfactor over a 21 day period.

The vehicle utilized in preparing the composition is notcritical. The vehicle may be any cosmetically acceptable vehicle which does not denature the transferfactorand which is non-toxic. It has been found that unscented moisturizing formulas generally utilized for dry skin care are suitable. Such moisturizing formulas generally are water and oil emulsions in which the transferfactor can be dispersed. Preferably, the vehicle is a lyophile non-toxic base. One such vehicle utilized in the following case studies is a Eucerin moisturizing formula obtained from Beiersdorf, Inc. of South Norwalk, Connecticut. The Eucerin moisturizing formula is a water in oil emulsion and is identified as containing water, petrolatum, mineral oil, mineral wax, wool wax alcohol and 2 - bromo - 2 nitropropane 1,3, diol.

The following case studies demonstrate the positive results obtained byutilizingthetransferfactorcom- position prepared in accordance with the invention.

The transferfactor utilized was prepared by utilizing scale-up techniques of the procedure outlined above which permit purification of large numbers of lympho cytes which are purified by common extraction utlizing the adherence ofgranulocytesto glass wool fibres. This permits harvesting from a mixed leukocyte preparation of 90% plus purified lymphocytes. The lymphocytes were then analyzed as to quantity and theircytoplasmic contents were obtained by destroying the cell walls using ultrasonictechniques. The transferfactorwasthen obtained from thecytoplasmic extraction, concentrated and passed through a molecular sieve which harvested only those fractions of molecularweightwhich include the transfer factor.

The following case studies utilized transferfactor prepared in accordance with this procedure dispersed in a Eucerin base with 5% DMSO added. Each of these case studies covered a period ofaboutthree months.

They are setforth as illustrative and not in a limiting sense.

Case 1 Female patient A had herpes simplex outbreaks for about three years in the vagina and vulva on a monthly basis preceeding menstruation. The ointment was applied to the infected area on the basis offourtimes per day. Within 24 hours all pain and irritation had ceased. Within 48 hours significant healing of the lesions was observed. By 72 hours all lesions had cleared. No recurrence to date.

Case 2 Female patient B had weekly buccal herpes simplex lesions for overfouryears. The patient applied the ointment to the infected sites on the basisoffourtimes per day. Within 24 hours all local irritation symptoms were abolished. Within 48 hours the lesions had disappeared. There have been no recurrent problems to date.

Case 3 Male patient C had multiple condylomatous growth about the neck area for several years which required periodic removal by hyfrication for control. The patient applied the ointment to the condylomata on the basis offourtimes per day. Within 24 hours all discomfort and irritation was significantly reduced.

With four days most of the condylmatous growth had disappeared. By the end oftwo weeks all the condylomatous growth had disappeared. No recurrence has been experienced to date.

Case 4 Male patient D had multiple condylomata on the fingers of both hands for at leasttwo years. The patient applied the ointment on the basis offourtimes per dayto the affected areas. At 48 hours there was a visible diminution in the size ofthe lesions. All lesions were cleared by the end of 14 days. There has been no recurrence ofthe lesions to date.

Case 5 Female patient E had a herpes simplex infection of the vulva and vagina for a period of overfiveyears with outbreaks occuring every two to three months.

The patient applied the ointmentto the lesions and surrounding areas at leastfourtimes per day. All pain and irritation were greatly reduced within the first 24 hours. Within 48 hours major healing had occurred.

No recurrence problems have been reported to date.

Case 6 Female patient F reported recurrent outbreaks of buccal herpes simplexfor abouttwo years. The ointment was applied to the lesions on the basis of fourtimes per day. Discomfort and pain disappeared within 24 hours. By 48 hours significant healing of the lesions was observed. At the end of 96 hours all lesions were cleared. No recurrence has been observed to date.

It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained and, since certain changes may be made in carrying outthe above method and in the composition set forth without departing from the spirit and scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

It is also understood thatthefollowing claims are intended to cover all ofthe generic and specific features of the invention which, as a matter of language, might be said to fall therebetween.

Particularly it isto be understood that in said claims, ingredients or compounds recited in the singular are intended to include compatible mixture of such ingredientswhereverthesense permits.

Claims (14)

1. Atopical composition fordermatological treatment comprising a vehicle and an effective amount of transferfactor dispersed therein.

2. The topical composition of claim 1, further including an effective amount of an enhancing penetrant.

3. The topical composition of claim 1, wherein the vehicle is a non-toxic lyophilic base.

4. The topical composition of claim 1,wherein the transfer factor is present in the amount of up to about 10 Units (1 o8 cells per Unit) per gram of composition.

5. The topical composition of claim 4, further including an effective amount of an enhancing penetrant.

6. The topical composition of claim 5, wherein the penetrant is selected from the group consisting of dimethyl sulfoxide, low molecular weight dextran, and mixtures thereof.

7. The topical composition of claim 6, wherein the penetrant is present up to about 15 percent by weight, based on the total weight ofthe composition.

8. The topical composition of claim7,wherein the penetrant is dimethyl sulfoxide.

9. The topical composition of claim 7, wherein the penetrant is a low molecularweight dextran.

10. Atopical composition forthetreatment of herpes simplex comprising a non-toxic lyophile base between about 1 and 10 Units (10cells per Unit) per gram of composition and about 1 and 15 percent by weight of dimethyl sulfoxide.

11. A method of improving the cosmetic appearance of the skin comprising applying to the skin a topical composition in accordance with any one of claims 1 to 10.

12. The method of claim 11, wherein the composition is applied to the skin between three and fourtimes per day.

13. The method of claim 11, wherein the composition includes about 1 Unit oftransferfactor per gram of composition.

14. Atopical cosmetic composition comprising a non-toxic lyophilic base and transferfactor dispersed therein.